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UCSC Genome Browser Gene Interaction Graph
Gene interactions and pathways from curated databases and text-mining

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AKT2 — INS

Pathways - manually collected, often from reviews:

Text-mined interactions from Literome

Whelan et al., J Biol Chem 2010 (Insulin Resistance) : Regulation of insulin receptor substrate 1 (IRS-1)/AKT kinase mediated insulin signaling by O-Linked beta-N-acetylglucosamine in 3T3-L1 adipocytes
Filho et al., Eur J Pharmacol 2013 (Hypertrophy, Left Ventricular...) : Insulin induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin stimulated serine/threonine kinase ( AKT ) and is severely impaired in obese, hypertensive rodents and humans
Khan et al., J Biol Chem 2006 : Endogenous IP3Rs in Chinese hamster ovary T-cells were phosphorylated in response to Akt activation by insulin
Jang et al., Life Sci 2010 (Insulin Resistance) : BSP significantly restored the suppression of insulin mediated Akt phosphorylation in insulin-resistant cells
Sasaki-Suzuki et al., J Biol Chem 2009 (Insulin Resistance) : In addition, insulin stimulated Akt phosphorylation was inhibited by GH pretreatment ... Moreover, small interfering RNA mediated IRS-2 knockdown also inhibited insulin stimulated Akt activation and glucose uptake without affecting GLUT4 translocation and plasma membrane fusion
Maeno et al., J Biol Chem 2012 (Metabolic Diseases) : Thr-86 of p85/PI3K was identified to be phosphorylated by PKC activation and confirmed to affect IRS1 mediated activation of Akt/eNOS by insulin and VEGF using a deletion mutant of the Thr-86 region of p85/PI3K
Giani et al., J Gerontol A Biol Sci Med Sci 2008 : GHRKO mice exhibited marked increases in the insulin induced phosphorylation of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), Akt , and ERK1/2 along with elevated insulin stimulated IRS-1 associated regulatory subunit of phosphatidylinositol 3-kinase in the heart
Muñoz et al., J Hypertens 2006 (Disease Models, Animal...) : We found that in the livers of OZR long-term administration of irbesartan is associated with : ( i ) increased insulin stimulated insulin receptor tyrosine phosphorylation ; ( ii ) decreased insulin receptor Ser994 phosphorylation ; ( iii ) augmented insulin receptor substrate (IRS) 1 and 2 abundance and tyrosine phosphorylation ; ( iv ) augmented association between IRS and the p85 regulatory subunit of phosphatidylinositol 3-kinase ; ( v ) increased insulin induced Akt phosphorylation ; and ( vi ) decreased hepatic steatosis
Nakajima et al., J Biol Chem 2000 (Carcinoma, Hepatocellular) : The high glucose treatment attenuated insulin induced association of IRS-1 and phosphatidylinositol 3-kinase and insulin stimulated phosphorylation of Akt
Carey et al., PloS one 2013 (Diabetes Mellitus, Type 2...) : Insulin stimulated Akt phosphorylation in human skeletal myotubes exposed to conditioned media was unaltered by either treatment condition
Lee et al., Am J Physiol Heart Circ Physiol 2010 (Disease Models, Animal...) : In myocardium, insulin stimulated glucose uptake, PI 3-kinase activation, and Akt phosphorylation were also blunted in the intervention diet group
Ha et al., Exp Mol Med 2005 (Insulin Resistance) : We investigated glucose uptake and the translocation of Akt and caveolin-3 in response to insulin in H9c2 cardiomyoblasts exposed to an experimental insulin resistance condition of 100 nM insulin in a 25 mM glucose containing media for 24 h ... In addition to a reduction in insulin induced Akt translocation to membranes, we observed a significant decrease in insulin stimulated membrane association of phosphorylated Akt with a consequent increase of the cytosolic pool ... As a result, insulin stimulated Akt activation in caveolae was significantly decreased
Gosmanov et al., Diabetes 2002 : PI 3-kinase inhibitors also abolished insulin stimulated p38 MAPK phosphorylation in the plantaris muscle and Akt phosphorylation in both muscles
Park et al., Exp Mol Med 2005 (Insulin Resistance) : These results suggest that the increase of O-GlcNAc modification on insulin signal pathway intermediates, such as IRS-1 and Akt2, reduces the insulin stimulated phosphorylation of IRS-1 and Akt2 , subsequently leading to insulin resistance in rat primary adipocytes
Baum et al., Am J Physiol Endocrinol Metab 2009 : Compared with control livers, insulin stimulated Akt phosphorylation and mTORC1 signaling, as assessed by increased phosphorylation of the mTORC1 targets eIF4E binding protein ( 4E-BP ) 1 and ribosomal protein S6 kinase (S6K)1, and promoted assembly of the eIF4G x eIF4E complex
Li et al., J Mol Cell Cardiol 2009 (Myocardial Reperfusion Injury) : In cultured endothelial cells subjected to simulated ischemia/reperfusion, insulin ( 10 ( - ) ( 7 ) M ) increased Akt activity and eNOS phosphorylation with subsequent NO production, and concurrently exerted an anti-adhesive effect as manifested by reduced endothelial P-selectin and ICAM-1 surface expression and PMNs adherence ( 13.7+/-1.3 % vs. 22.2+/-1.9 % in vehicle, n=9, P < 0.01 ), all of which are abolished by the specific Akt inhibitor
Yuzefovych et al., Am J Physiol Endocrinol Metab 2010 (Insulin Resistance) : Oleate alone did not cause mtROS generation and mtDNA damage, and its addition to palmitate prevented palmitate induced mtDNA damage, increased total ATP levels and cell viability, and prevented palmitate induced apoptosis and inhibition of insulin stimulated Akt ( Ser ( 473 ) ) phosphorylation
Kim et al., Contrast Media Mol Imaging 2013 (MAP Kinase Signaling System) : Magnetic labeling of pancreatic ß-cells modulates the glucose- and insulin induced phosphorylation of ERK1/2 and AKT ... This study demonstrates that SPIO labeling alters some fundamental functional variables, at least in INS-1 cells, through modulation of the glucose- or insulin induced activation of ERK1/2 and AKT , which leads to insulin biosynthesis
Kurowski et al., Diabetes 1999 (Hyperglycemia) : Hyperglycemia inhibits insulin activation of Akt/protein kinase B but not phosphatidylinositol 3-kinase in rat skeletal muscle
Song et al., Diabetes 1999 (Body Weight...) : Maximal insulin stimulated Akt ( protein kinase B ) kinase activity is decreased in soleus muscle from GK rats and restored upon normalization of glycemia ( Krook et al., Diabetes 46 : 2100-2114, 1997 ) ... Here, we show that in EDL muscle from GK rats, maximal insulin stimulated Akt kinase activity is also impaired and restored to Wistar rat levels after phlorizin treatment
Cseh et al., Orv Hetil 2009 (Diabetes Mellitus...) : Akt activation is regulated by growth factors, insulin , and also environmental factors as altered oxygen tension and high temperature
Morisco et al., Cardiovasc Res 2007 (Insulin Resistance) : Furthermore, concomitant activation of Akt , ERK 1/2, and JNK was required for insulin to exert its protective effect against the hypoxia induced cleavage of caspase-3
Massao Hirabara et al., FEBS Lett 2003 : Palmitate reduced insulin stimulated phosphorylation of insulin receptor substrate-1/2, Akt , and p44/42 mitogen activated protein kinases
Zhao et al., Ethn Dis 2010 (Cardiomegaly) : This was also relevant to I ( K ) functional density which was reduced by activation of both MAPKs and Akt by angiotensin II (ANG II) and insulin-like growth factor-1 (IGF-1) , respectively ; however, this reduction was reversed by inhibition of PI-3K alone in hypertrophied myocytes but not in normal ones
Fang et al., Exp Neurol 2007 (Alcohol-Induced Disorders, Nervous System...) : Acetaldehyde suppressed basal and insulin stimulated Akt phosphorylation without affecting total Akt expression
Xu et al., PloS one 2010 : SRA in adipocytes increases both glucose uptake and phosphorylation of Akt and FOXO1 in response to insulin
Filippi et al., Cell Metab 2012 (Hyperinsulinism...) : Insulin activates PI3-kinase (PI3K)/AKT to regulate glucose homeostasis in the peripheral tissues and the mediobasal hypothalamus ( MBH ) of rodents
Brozinick et al., J Biol Chem 1998 : Insulin , but not contraction, activates Akt/PKB in isolated rat skeletal muscle ... However, Akt kinase activity was significantly stimulated by insulin and not contraction ... Moreover, wortmannin, an inhibitor of PI 3'-kinase, completely blocked the insulin stimulated increase in Akt activity and glucose transport but did not alter either of these parameters in contracting muscles
Hua et al., Diabetes 2013 (Cardiomegaly...) : Additionally, cathepsin K knockout alleviated whole-body glucose intolerance and improved insulin stimulated Akt phosphorylation in high-fat diet fed mice
Hermann et al., Arterioscler Thromb Vasc Biol 2000 : Insulin mediated stimulation of protein kinase Akt : A potent survival signaling cascade for endothelial cells ... The present study demonstrates an important role for insulin mediated Akt activation in the prevention of endothelial cell apoptosis, which may importantly contribute to cell homeostasis and the integrity of the endothelium
Arcaro et al., Biochem J 2007 (Brain Neoplasms) : Insulin potently activated Akt ( also called protein kinase B ) in AT/RT cells, as compared with other growth factors, such as epidermal growth factor
Rhodes et al., Cancer Res 2008 (Neoplasms) : Consistent with the role of Akt in insulin signaling, treatment with GSK690693 resulted in acute and transient increases in blood glucose level
Ueki et al., J Biol Chem 2003 : p85 beta-/- cells, however, exhibit significantly increased insulin induced Akt activation, leading to increased anti-apoptosis
Li et al., Crit Care Med 2008 (Reperfusion Injury) : In cultured cardiomyocytes subjected to SI/R, insulin reduced TNF-alpha induction and increased Akt and endothelial nitric oxide synthase (eNOS) phosphorylation and subsequent nitric oxide ( NO ) production
Gao et al., Zhonghua Nei Ke Za Zhi 2003 (Myocardial Reperfusion Injury) : Both insulin induced Akt activation and anti-apoptotic effect could be abrogated by wortmannin, a phosphatidylinositol (PI) 3-kinase inhibitor
Tanigaki et al., Circ Res 2009 : In endothelial cells we find that CRP attenuates insulin induced Akt phosphorylation, and CRP antagonism of eNOS is negated by expression of constitutively active Akt ; the inhibitory effect of CRP on Akt is also observed in vivo
Henkel et al., Lab Invest 2011 (Fatty Liver...) : OSM in turn attenuated insulin dependent Akt activation and, as a downstream target, glucokinase induction in hepatocytes, most likely by inducing suppressor of cytokine signaling 3 ( SOCS3 )
Dan et al., J Immunol 2008 : Insulin activation of mTOR requires Akt in a manner that involves IKKalpha, preferentially to IKKbeta, and TSC2 phosphorylation
Zhao et al., Schizophr Res 2006 (Diabetes Mellitus, Type 2...) : The goal of the present studies was to assess the role of insulin dependent Akt signaling in schizophrenia and in animal and cellular models of insulin resistance ... The results suggest that alterations in insulin dependent Akt signaling in schizophrenia are similar to those observed in our cellular but not animal models of insulin resistance
Zhou et al., Eur J Pharmacol 2009 : We show in the current study that transient overexpression of PC-1 inhibits insulin stimulated insulin receptor tyrosine phosphorylation in HEK293 cells, while knockdown of PC-1 with siRNA significantly increases insulin stimulated Akt phosphorylation in HuH7 human hepatoma cells
Gao et al., J Pharmacol Exp Ther 2012 (Neovascularization, Pathologic...) : L-4F had no effect on the insulin induced phosphorylation of Akt , but inhibited the activation of extracellular signal regulated kinase and p70s6 kinase, leading to the inhibition of HIF-1a synthesis
Drapeau et al., Am J Physiol Endocrinol Metab 2013 (Diabetic Nephropathies...) : Elevated SHP-1 expression induced by high glucose levels was directly associated with insulin receptor-ß in vitro and in vivo to prevent insulin stimulated Akt and ERK phosphorylation
Annerén et al., Mol Med 2002 : In RINm5F cells, the diminished IRS-phosphorylation was accompanied by a reduced insulin stimulated activation of phosphatidylinositol 3-kinase (PI3K), AKT and Extracellular Signal Regulated Kinase, partly due to an increased basal activity
Yang et al., FEBS Lett 2005 : At the molecular level, Cr ( pa ) 3 enhanced insulin stimulated phosphorylation of Akt in a time- and concentration dependent manner without altering the phosphorylation of insulin receptor
Baudhuin et al., Mol Pharmacol 2002 : Insulin , on the other hand, stimulates Akt S473 phosphorylation independent of both MEK and p38 in HEY cells
Ding et al., Exp Cell Res 2008 : TRB3 negatively regulates Akt activation and noticeably, TRB3 expression is induced by insulin
Naruse et al., Diabetes 2006 (Atherosclerosis...) : Insulin stimulated increases in Akt phosphorylation and cGMP concentration ( a measure of NO bioavailability ) after euglycemic-hyperinsulinemic clamp were blunted in the aorta of fatty compared with lean rats but were partly normalized after 2 weeks of treatment with the PKCbeta inhibitor ruboxistaurin ( LY333531 ) ... In endothelial cell culture, overexpression of PKCbeta1 and -beta2, but not PKCalpha, -delta, or -zeta, decreased insulin stimulated Akt phosphorylation and eNOS expression ... Thus, activation of PKCbeta in endothelial cells and vascular tissue inhibits Akt activation by insulin and VEGF, inhibits Akt dependent eNOS regulation by insulin , and causes endothelial dysfunction in obesity associated insulin resistance
Famulla et al., Int J Obes Relat Metab Disord 2011 (Inflammation...) : Treatment of adipocytes and hSkMC with PEDF induced insulin resistance in adipocytes, skeletal and smooth muscle cells at the level of insulin stimulated Akt phosphorylation, which was dose dependent and more prominent in adipocytes
Arias et al., Diabetes 2004 (Insulin Resistance) : Previous research in 3T3-L1 adipocytes indicated that insulin stimulated glucose uptake and phosphorylation of Akt were reduced after incubation with O- ( 2-acetamido-2-deoxy-D-glucopyranosylidene ) amino-N-phenylcarbamate ( PUGNAc ; 100 micromol/l ), an inhibitor of the O-GlcNAcase that catalyzes removal of O-GlcNAc from proteins ... PUGNAc did not significantly alter insulin stimulated phosphorylation of Akt ( serine and threonine ) or its substrates glycogen synthase kinase (GSK)3 alpha and GSK3 beta
Mistafa et al., Biochem Biophys Res Commun 2008 : These data indicate that extracellular ATP and statins via the P2X7 receptor modulate insulin induced Akt signaling in epithelial cells
Kamon et al., Biochem Biophys Res Commun 2004 (Body Weight...) : Using dominant negative mutants of Akt or PKClambda ( downstream effectors of phosphoinositide 3-kinase ), insulin stimulated Akt activity was found to be important in the regulation of adiponectin secretion by insulin in 3T3-L1 adipocytes ... These observations suggest that `` insulin stimulated Akt activity in adipocytes '' may play an important role in the regulation of adiponectin secretion
Zhou et al., Zhejiang Da Xue Xue Bao Yi Xue Ban 2004 (Insulinoma...) : Nelfinavir decreased insulin stimulated phosphorylation of IRS-2 and Akt-Thr ( 308 ) in a dose dependent manner ; for 10 micromol/L of nelfinavir, the decrease was 52 % and 55 %, respectively
Mughal et al., Diabetologia 2010 (Hyperplasia) : C-peptide did not affect insulin induced Akt or extracellular signal regulated kinase signalling ( 15 min ), but array data and gene silencing implicated sterol regulatory element binding transcription factor 1 ( SREBF1 )
Ueda et al., Exp Cell Res 2004 : Insulin , a major survival factor in many cells, strongly increased phosphorylation of Akt , which was completely blocked by carbachol ... These results demonstrate that Gq/11 signaling induces apoptosis by reducing insulin stimulated Akt phosphorylation through tyrosine dephosphorylation and activating RhoA in HeLa cells
Thorn et al., Diabetes 2013 (Fetal Growth Retardation) : Insulin robustly activated AKT , GSK3ß, and forkhead box class O (FOXO)1 in CON and IUGR fetal livers
Kim et al., Diabetes 2002 (Diabetes Mellitus, Type 2) : Insulin stimulated Akt activity also increased after troglitazone treatment ( from 32 +/- 8 to 107 +/- 32 % stimulation, P < 0.05 ) but was unchanged after metformin therapy
Tonks et al., Diabetologia 2013 (Diabetes Mellitus, Type 2...) : Insulin stimulated Akt phosphorylation at Thr309 and Ser474 was highly correlated with whole-body insulin sensitivity
Wijesekara et al., Mol Cell Biol 2005 (Diabetes Mellitus...) : Deletion of muscle Pten resulted in enhanced insulin stimulated 2-deoxyglucose uptake and Akt phosphorylation in soleus but, surprisingly, not in extensor digitorum longus muscle compared to littermate controls upon high-fat feeding, and these mice were spared from developing hyperinsulinemia and islet hyperplasia
Pandolfi et al., Arterioscler Thromb Vasc Biol 2005 (Atherosclerosis...) : Insulin effects on NO release and Akt phosphorylation were significantly impaired in fibroblasts from IR as compared with IS individuals
Rui et al., J Biol Chem 2001 (Carcinoma, Hepatocellular...) : By contrast, IRS-1 activation of Akt and ERK1/2 was not inhibited by chronic insulin/IGF-1 stimulation in IRS-2-deficient mouse embryo fibroblasts
Subramanian et al., J Cell Biochem 2006 : In contrast, insulin induced small increases in system A activity and large increases in phospho-Akt levels
Wada et al., Eur J Pharmacol 2013 (Chronic Disease...) : Cilostazol also effectively ameliorated the TNFa induced decrease of insulin stimulated Akt phosphorylation and [ ( 3 ) H ] 2-deoxyglucose uptake by suppressing c-Jun N terminal kinase mediated serine phosphorylation of insulin receptor substrate 1 in 3T3-L1 adipocytes
Tabbi-Anneni et al., Endocrinology 2008 (Body Weight...) : Rates of fatty acid oxidation were increased and glycolysis decreased in ob/ob hearts, and insulin did not modulate substrate use in hearts of ob/ob mice and did not increase Akt phosphorylation
Goto et al., Reproduction 2009 : Pretreatment with hCG attenuated insulin-like growth factor (IGF)-1 induced phosphorylation of AKT and cell proliferation, not phosphorylation of ERK1/2
Saha et al., Diabetes 2010 (Insulin Resistance) : Incubation of the EDL with the higher concentrations of both leucine and glucose also caused insulin resistance, reflected by a decrease in insulin stimulated Akt phosphorylation
Mounier et al., Endocrinology 2006 : In contrast, 1 nm insulin inhibited the IGFBP-1 mRNA level by 40 % and correspondingly activated Akt and Foxo1/Foxo3 phosphorylation to a level comparable to that observed with 100 nM insulin
Andreelli et al., Endocrinology 2006 (Disease Models, Animal...) : This was confirmed in vivo by normal insulin induced phosphorylation of Akt and transcriptional regulation of the phosphoenolpyruvate carboxykinase, glucose-6 phosphatase, and pyruvate kinase in liver during the fasted/fed transition
Bhattacharyya et al., Diabetologia 2012 (Glucose Intolerance...) : Carrageenan exposure completely inhibited insulin induced increases in phospho- ( Ser473 ) -Akt and PI3K activity in vivo in mouse liver and in human HepG2 cells
Hu et al., Eur J Pharmacol 2008 : RANKL induced Akt phosphorylation was strongly inhibited by berberine ; however, neither monocyte/macrophage-colony stimulating factor ( M-CSF ) -induced nor insulin induced Akt activation was inhibited by the drug
Chandrasekher et al., Invest Ophthalmol Vis Sci 2003 : Whereas there was a gradual decrease in insulin/IGF-1 mediated activation of PI-3K and its downstream target Akt , with progression of differentiation in chicken lens epithelial cells, Erk2 phosphorylation induced by these growth factors was not decreased ; rather, it remained increased in early stages of differentiation
Sharma et al., Am J Physiol Regul Integr Comp Physiol 2012 (Insulin Resistance) : The most consistent and robust effect of moderate calorie restriction ( CR ; ~60 % of ad libitum, AL, food consumption ) on insulin signaling in rodent muscle has been enhanced insulin induced phosphorylation of Akt ( pAkt )
Izawa et al., Exp Cell Res 2005 (Hypertension...) : Ang II inhibition of insulin stimulated IRS-1 tyrosyl phophorylation and Akt activation were reversed by PD98059 but not by SP600125
Wong et al., Atherosclerosis 2006 (Body Weight...) : Insulin stimulated phosphorylation of Akt/PKB was significantly increased in skeletal muscle of ATORVA_50 versus CONT in both lean and fatty rats
Tamura et al., Diabetologia 2007 (Diabetes Mellitus...) : The treatment was associated with improved glucose tolerance, reduction in the serum insulin level, and increased hepatic triacylglycerol and glycogen contents, but had no effect on insulin stimulated phosphorylation of Akt
Haque et al., Cell 2011 : Expression of conformation-sensor scFvs as intracellular antibodies ( intrabodies ) enhanced insulin induced tyrosyl phosphorylation of the ß subunit of the insulin receptor and its substrate IRS-1 and increased insulin induced phosphorylation of PKB/AKT
Kwintkiewicz et al., Fertil Steril 2006 : In contrast, mevastatin had no significant effect on either basal or insulin induced phosphorylation of Akt/PKB
Zeng et al., J Bioenerg Biomembr 2012 : The results showed that NYGGF4 knockdown dramatically activate the insulin stimulated phosphorylation of IRS-1 and AKT
Tajmir et al., J Cell Physiol 2003 : However, despite insulin stimulated glucose uptake being unaffected upon 24 h preincubation with leptin, a small but significant decrease ( 37 % ) in insulin stimulated GLUT4 translocation and phosphorylation of Akt on T308 was detected ... Insulin stimulated phosphorylation of Akt on S473 or of p38 MAPK were unaffected
Sharma et al., Mol Cell Biol 1997 : Interestingly, overexpression of either PTB or SAIN protein did not affect insulin induced AKT activation or insulin stimulated 2-deoxyglucose transport, even though both of these bioeffects are inhibited by wortmannin ... In 3T3-L1 adipocytes, interference with the IR-IRS-1 interaction did not cause inhibition of insulin stimulated AKT activation or glucose transport
Jia et al., Nature 2008 (Cell Transformation, Neoplastic...) : Using established mouse embryonic fibroblasts, we found that removal of p110beta also had little effect on Akt phosphorylation in response to stimulation by insulin and epidermal growth factor, but resulted in retarded cell proliferation
Carricaburu et al., Proc Natl Acad Sci U S A 2003 : PIP4K II beta expression did not impair insulin dependent association of PI3K with insulin receptor substrate 1 (IRS1) but abbreviated Akt activation, indicating that PIP4K II regulates PI-3,4,5-P3 degradation rather than synthesis
Motaghedi et al., Obesity (Silver Spring) 2008 (Insulin Resistance) : Consistent with these results we found that insulin stimulated phosphorylation of the protein kinase Akt was increased by 2-AG, attenuated by SR141716, and unaffected in the absence of insulin or by addition of high-dose insulin ... These data provide a functional and molecular link between the CB1 receptor and insulin sensitivity, because insulin stimulated phosphorylation of Akt is required for GLUT4 translocation to the PM
De Vita et al., Cancer Res 2000 (Cell Transformation, Neoplastic) : Given that thyrotropin and insulin stimulate Akt activation in thyroid cells, we set out to determine the effects of Akt on thyroid cell proliferation, survival, and differentiation
Kobashi et al., Journal of inflammation (London, England) 2009 : Furthermore, we examined the effect of IL-8 on the phosphorylation of Akt induced by insulin ... The IL-8 inhibited insulin induced Akt phosphorylation ... These data suggest that IL-8 is a main adipocytokine producing insulin resistance via the inhibition of insulin induced Akt phosphorylation in adipocytes
Niu et al., Sci China C Life Sci 2007 : The phosphorylation of Akt in these two cell lines was increased by insulin
Xue et al., Biochem Biophys Res Commun 2011 (Diabetes Mellitus, Type 2) : Prolonged inorganic arsenite exposure suppresses insulin stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes : involvement of the adaptive antioxidant response
Grempler et al., Diabetes 2007 : Liver-specific expression of a dominant negative SHIP2 mutant in KKA ( y ) mice increased basal and insulin stimulated Akt phosphorylation
Dong et al., Diabetes 2005 (Glucose Intolerance...) : In liver of PC-1 animals, insulin stimulated IR tyrosine kinase and Akt/protein kinase B activation were both decreased
Kang et al., Metabolism 2012 (Inflammation...) : Insulin stimulated insulin receptor substrate-1 tyrosine phosphorylation ( Y612 ) was suppressed in RSV treated adipocytes compared with untreated adipocytes, as was the insulin stimulated Akt phosphorylation ( Ser473 ) ... However, under an insulin-resistant condition that was made by incubating 3T3-L1 adipocytes in the conditioned medium from lipopolysaccharide stimulated LAW264.7 cells, RSV reduced inducible nitric oxide synthase expression and I?Ba protein degradation and improved insulin stimulated Akt phosphorylation ( Ser473 ) ... The insulin stimulated Akt phosphorylation was decreased in the liver and white adipose tissue of DIO mice, but it was completely normalized by RSV treatment
Brennesvik et al., Cell Signal 2005 : Here we find that adrenaline alone did not influence PKB activation, but adrenaline dramatically potentiated insulin stimulated phosphorylation of PKB ( both Ser473 and Thr308 ) and of PKBalpha and PKBbeta enzyme activities
Cleasby et al., J Endocrinol 2011 (Insulin Resistance) : These effects are likely explained by APPL1 OE-induced increase in basal and insulin stimulated phosphorylation of IRS1, AKT , GSK3ß and TBC1D4
Tan et al., J Biol Chem 2012 (Insulin Resistance) : Akt plays a major role in insulin regulation of metabolism in muscle, fat, and liver
Cariou et al., J Biol Chem 2006 (Insulin Resistance) : In parallel, FXR deficiency alters distal insulin signaling, as reflected by decreased insulin dependent Akt phosphorylation in both white adipose tissue and skeletal muscle
Trümper et al., Ann N Y Acad Sci 2000 : Insulin , IGF-1, and GLP-1 induced distinctive time dependent, dose dependent, and glucose dependent phosphorylation of PKB/Akt
He et al., J Biol Chem 2003 (MAP Kinase Signaling System) : Expression of FLNaCT had no major effect on insulin induced phosphorylation of the IR, insulin receptor substrate-1, or AKT , but it elicited changes in actin cytoskeletal structure and ruffle formation in HepG2 cells
Katakam et al., J Cereb Blood Flow Metab 2012 (Insulin Resistance) : Immunoblot experiments revealed that insulin induced phosphorylation of Akt , endothelial NOS, and expression of GTP cyclohydrolase-I (GTP-CH) were diminished, but phosphorylation of PKC and ERK was enhanced in ZO arteries
Hwang et al., Biochem Biophys Res Commun 2013 (Insulin Resistance) : Tan IIA clearly suppressed the phosphorylations of PERK and JNK and potentiated insulin mediated Akt phosphorylation as well as glucose uptake via AMPK activation under ER stress
Bouraoui et al., Am J Physiol Regul Integr Comp Physiol 2010 : AKT phosphorylation increased in the presence of both insulin and IGF-I, with higher levels of stimulation in adipocytes than in preadipocytes
Eringa et al., Am J Physiol Endocrinol Metab 2007 (Insulin Resistance...) : Protein analysis of resistance arteries revealed that insulin mediated activation of Akt was preserved in obese rats, whereas expression of eNOS was markedly decreased
Park et al., Biochemistry 1999 : Insulin and IGF-1 receptors activate Akt to a similar extent, whereas GSK-3 inactivation in response to IGF-1 is considerably lower in both -/- and WT cells, compared to the effect of insulin in WT cells
Kaifu et al., Nephrol Dial Transplant 2009 : Furthermore, insulin ( 1-100 nmol/L ) dose-dependently stimulated Akt phosphorylation ... Treatment with the phosphatidylinositol 3-kinase inhibitors wortmannin ( 100 nmol/L ) and LY294002 ( 10 micromol/L ) attenuated insulin induced Akt phosphorylation, indicating that insulin phosphorylates Akt via a phosphatidylinositol 3-kinase dependent pathway
Freund et al., Stem Cells 2008 : Since insulin triggered sustained phosphorylation of Akt in hESC, we analyzed the effect of an Akt inhibitor during coculture
Liu et al., J Biol Chem 2012 (Insulin Resistance...) : In addition, suppressing PKCa expression by shRNA in hepatocytes reduces ER stress induced APPL1 phosphorylation at Ser ( 430 ) as well as the inhibitory effect of ER stress on insulin stimulated Akt phosphorylation ... Consistent with a negative regulatory role of APPL1 phosphorylation at Ser ( 430 ) in insulin signaling, overexpression of APPL1 ( S430D ) but not APPL1 ( S430A ) impairs the potentiating effect of APPL1 on insulin stimulated Akt phosphorylation at Thr ( 308 )
Villafuerte et al., Endocrinology 2009 (Diabetes Mellitus, Type 2...) : We previously identified the insulin-response element binding protein-1 ( IRE-BP1 ) as an effector of insulin induced Akt signaling in the liver, and showed that the 50-kDa carboxyl fragment confers the transcriptional activity of this factor
Chai et al., Peptides 2009 : NDP-MSH augmented insulin stimulated AKT phosphorylation in vitro ... The melanocortin agonist melanotan II increased insulin stimulated AKT phosphorylation in the rat hypothalamus in vivo
Chai et al., J Neuroendocrinol 2013 : AGD3 binds with insulin receptor substrate 4 and increases insulin stimulated phospho-Akt and regulates AMP activated protein kinase and mammalian target of rapamycin downstream target S6 kinase phosphorylation
Holt et al., Mol Endocrinol 2009 : In this study we utilize compound gene knockout mice to demonstrate that although deficiency in one adaptor can enhance insulin induced IRS-1 phosphorylation and Akt activation , insulin signaling is not increased further upon dual ablation of Grb10 and Grb14
Chen et al., PloS one 2012 (Body Weight...) : Second, biochemical analyses revealed constitutively elevated JNK activity and diminished insulin induced AKT activation in the liver of SERT-deficient mice
Ikemura et al., Mol Pharm 2010 (Body Weight...) : Treatment of 3T3-L1 adipocytes with glucose oxidase ( GO ) increased lipid hydroperoxide formation and reduced insulin stimulated Akt phosphorylation
Göransson et al., Cell Signal 2002 : Ser-474 is the major target of insulin mediated phosphorylation of protein kinase B beta in primary rat adipocytes ... In this study, we have characterized the insulin induced phosphorylation and activation of PKB beta in primary rat adipocytes ... Insulin stimulation resulted in a translocation of PKB beta from cytosol to membranes, and phosphorylation and activation of PKB beta ... Taken together, these results show that rat adipocyte PKB beta mainly is phosphorylated on Ser-474 in response to insulin stimulation, in contrast to previous studies in human embryonic kidney (HEK) 293 cells demonstrating, in addition, phosphorylation of Thr-309
Sugita et al., Am J Physiol Endocrinol Metab 2005 (Burns...) : Burn injury impairs insulin stimulated Akt/PKB activation in skeletal muscle ... We therefore examined the effects of burn injury on insulin stimulated Akt/PKB activation in skeletal muscle ... Insulin stimulated phosphorylation of Akt/PKB was significantly attenuated in burned compared with sham burned rats ... Insulin stimulated Akt/PKB kinase activity, as judged by immune complex kinase assay and phosphorylation status of the endogenous substrate of Akt/PKB, glycogen synthase kinase-3beta ( GSK-3beta ), was significantly impaired in burned rats ... These results demonstrate that burn injury impairs insulin stimulated Akt/PKB activation in skeletal muscle and suggest that attenuated Akt/PKB activation may be involved in deranged metabolism and muscle wasting observed after burn injury
Wright et al., Cardiovasc Res 2009 (Disease Models, Animal...) : Insulin stimulated Akt/PKB and AS-160 phosphorylation were preserved, and PDH activity was unchanged
Stronach et al., Neoplasia (New York, N.Y.) 2011 (Carcinoma...) : Insulin mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors
Williams et al., Biochem Biophys Res Commun 2012 (Critical Illness...) : There was a reduction in insulin induced phosphorylation of IR, IRS-1, Akt and GSK-3ß
Baviloni et al., J Ethnopharmacol 2010 (Diabetes Mellitus, Experimental) : In the liver from diabetic treated group, the insulin stimulated AKT phosphorylation was higher and the PEPCK protein levels were reduced
Nawano et al., Biochem Biophys Res Commun 1999 (Body Weight...) : However, interestingly, insulin induced phosphorylation and kinase activation of Akt/PKB were severely suppressed ... In addition, impaired insulin induced Akt/PKB activation was also normalized
Kotani et al., Mol Cell Biol 1998 : These mutants did not inhibit insulin induced activation of Akt ... Furthermore, overexpression of an Akt mutant in which the phosphorylation sites targeted by growth factors are replaced by alanine resulted in inhibition of insulin induced activation of Akt but not of PKClambda
Jiang et al., Biochem J 2004 : In HEK-293 ( human embryonic kidney 293 ) cells stably expressing recombinant IRS1 and in 3T3L1 adipocytes, rosiglitazone attenuated PMA induced IRS1 S307/S612 phosphorylation and decreased insulin stimulated Akt phosphorylation
Zhang , Biochem J 2006 : Resveratrol effectively inhibits insulin induced Akt and MAPK ( mitogen activated protein kinase ) activation mainly through disruption of the interactions between insulin receptor substrates and its downstream binding proteins including p85 regulatory subunit of phosphoinositide 3-kinase and Grb2 ( growth factor receptor bound protein 2 )
Desouza et al., Diabetes 2011 (Diabetes Mellitus, Type 2...) : Modified EPCs exposed to TNF-a showed a lesser reduction ( RelA 20 % ) in insulin stimulated AKT phosphorylation versus a 55 % reduction in unmodified EPCs
Tsuchiya et al., Life Sci 2013 : Insulin activated Akt in adipocytes, but no Akt activation was induced by any investigated DAG
Yao et al., Pancreas 2002 (Pancreatic Neoplasms) : Insulin-like growth factor (IGF)-I induced Akt activation in a dose dependent manner and stimulated anchorage dependent and anchorage independent cell growth of PANC-1 cells
Gu et al., Insect Biochem Mol Biol 2009 : Phosphorylation of Akt and the insulin receptor was stimulated by insulin , and stimulation of Akt phosphorylation appeared to be PI3K dependent and developmentally regulated
Carvalheira et al., Endocrinology 2003 (Insulin Resistance...) : Conversely, insulin induced phosphorylation of Akt in heart was decreased in obese rats
Liu et al., J Biol Chem 2010 : Treating C2C12 cells with RSV dramatically inhibited insulin stimulated Akt , S6 kinase, and 4E-BP1 phosphorylation but had little effect on tyrosine phosphorylation of the insulin receptor and activation of the p44/42 MAPK signaling pathway
Nasrazadani et al., Genes & cancer 2011 : In vitro, knockdown of JNK2 or GAB2 inhibits Akt activation by hepatocyte growth factor (HGF), insulin , and heregulin-1, while phosphorylation of ERK is constitutive and Src dependent
Selim et al., Mol Immunol 2007 : Tribbles is a Drosophila protein that slows cell cycle progression, and its mammalian homolog, TRB3 interferes with insulin induced activation of AKT
Haugaard et al., Diabetes 2005 (Acquired Immunodeficiency Syndrome...) : Insulin stimulated Akt Ser473 and Akt Thr308 phosphorylation was decreased in LIPO patients ( P < 0.05 ), whereas insulin receptor substrate-1 associated phosphatidylinositol (PI) 3-kinase activity increased significantly ( P < 0.001 ) and similarly ( NS ) in both groups during clamp
Pellegatta et al., Int J Mol Med 2011 (Insulin Resistance) : Both insulin ( 100 ng/ml ) and ET-1 ( 10 nmol/l ) dose-dependently increased the phosphorylation of Akt and ERK1/2 ... Pre-treatment with ET-1 did not suppress the insulin induced Akt and ERK1/2 phosphorylation
Smith et al., Ann N Y Acad Sci 1999 (Diabetes Mellitus, Type 2...) : Downstream activation and serine phosphorylation of PKB/Akt by insulin were also markedly reduced in Type 2 diabetes
Takano et al., Diabetes 2001 (Insulin Resistance...) : Fractionation studies indicated that chronic GH treatment reduces insulin stimulated translocation of Akt from the cytosol to the plasma membrane
Natalicchio et al., Endocrinology 2010 : Moreover, exposure to TNFalpha resulted in increased serine phosphorylation of both insulin receptor substrate (IRS)-1 and IRS-2 and reduced basal and insulin induced Akt phosphorylation
Wei et al., J Biol Chem 2006 : Finally, small interfering RNA ( siRNA ) -specific gene silencing targeted specifically against p47phox ( p47siRNA ), in both L6 and primary myotubes, reduced the cognate protein expression, decreased NADPH oxidase activity, restored Ang II-impaired IRS1 and Akt activation as well as GLUT4 translocation by insulin
Bruss et al., Diabetes 2005 : Both insulin and contractions activate Akt in skeletal muscle ... P-Akt , PAS-160, and PAS-250 increased significantly with 0.6 nmol/l insulin
Ikonomov et al., Endocrinology 2002 : Expression of PIKfyveDeltaK and PIKfyve ( WT ) in Chinese hamster ovary T cells decreased or increased, respectively, insulin stimulated Akt phosphorylation at Ser473 but not at Thr308
Mu et al., Diabetes 2012 (Body Weight...) : Restoration of insulin sensitivity was demonstrated by the enhanced ability of insulin to induce Akt/protein kinase B phosphorylation in liver, muscle, and adipose tissues
Kato et al., Biochem Biophys Res Commun 2007 : Interacting with Ser/Thr protein kinases Akt, TRB3 impairs Akt activation induced by growth factors and insulin
O'Neill et al., Age (Dordrecht, Netherlands) 2010 (Atrophy) : Muscles from MIRKO mice demonstrated absent phosphorylation of AKT in response to exogenous insulin along with a failure to phosphorylate ribosomal S6 compared with lox/lox mice
Taghibiglou et al., J Biol Chem 2002 (Insulin Resistance) : Phosphatidylinositol 3-kinase activity as well as insulin stimulated Akt-Ser473 and Akt-Thr308 phosphorylation were also significantly reduced with fructose feeding
Krook et al., Diabetes 1998 (Diabetes Mellitus, Type 2) : Insulin stimulated Akt kinase activity is reduced in skeletal muscle from NIDDM subjects ... We examined the effect of insulin on Akt kinase activity in skeletal muscle from six NIDDM patients and six healthy subjects ... In both groups, insulin induced a significant increase in Akt kinase activity, but the response to maximal insulin ( 60 nmol/l ) was markedly reduced in skeletal muscle from NIDDM subjects ( 66 % of control levels, P < 0.01 ) ... These parallel defects in insulin stimulated Akt kinase activity and glucose transport in diabetic skeletal muscle suggest that reduced Akt kinase activity may play a role in the development of insulin resistance in NIDDM
Kwintkiewicz et al., Biol Reprod 2006 : Phosphorylation of AKT was stimulated by insulin only, while phosphorylation of MAPK3/1 and RPS6KB1 was increased by insulin and oxidative stress
Arteaga et al., American journal of physiology. Renal physiology 2005 : We demonstrate that Akt does not increase ENaC function under basal conditions or after stimulation with aldosterone, insulin , or AVP
Ivins Zito et al., J Cell Physiol 2004 : Whether SHP-2 regulates insulin-like growth factor-1 (IGF-1) dependent activation of Akt at the level of PI3K has yet to be established ... Here, we show that overexpression of a catalytically inactive mutant of SHP-2 inhibited insulin-like growth factor-1 (IGF-1) dependent PI3K and Akt activation
Frasca et al., J Biol Chem 2007 : Inhibition of c-Abl tyrosine kinase by STI571 attenuates the effect of insulin on Akt/GSK-3beta phosphorylation and glycogen synthesis, and at the same time, it enhances the effect of insulin on ERK activation, cell proliferation, and migration
Maffucci et al., Cancer Res 2005 (Ovarian Neoplasms) : Ins ( 1,3,4,5,6 ) P5 blocks FGF-2 mediated Akt phosphorylation and inhibits both survival and migration in HUVEC
Xu et al., Mol Endocrinol 2007 (Insulin Resistance...) : Next, anti-CD64 Fcgamma phagocytic receptor I ( FcgammaRI ), but not anti-CD16 ( FcgammaRIIIa ) or anti-CD32 ( FcgammaRII ) antibody, partially blocked the recombinant CRP induced phosphorylation of JNK and IRS-1 and restored, to a certain extent, the insulin stimulated phosphorylation of Akt
Fujiwara et al., J Physiol 2007 : Furthermore, we found that the V1b receptor was expressed in white adipose tissue and that insulin stimulated phosphorylation of Akt as an important signaling molecule was increased in adipocytes isolated from V1bR ( -/- ) mice
Xu et al., Horm Metab Res 2010 (Insulin Resistance) : Concomitantly, insulin induced activation of Akt/PKB and of ERK1/2 was strongly inhibited
Mauvais-Jarvis et al., J Clin Invest 2002 (Diabetes Mellitus, Experimental...) : Thus, despite the decrease in p85alpha, PI 3-kinase activation is normal, insulin stimulated Akt activity is increased, and glucose tolerance and insulin sensitivity are improved
Weigert et al., J Biol Chem 2006 : This Ser-318 phosphorylation improved insulin stimulated Akt phosphorylation and glucose uptake in myotubes since transfection with an IRS-1/Glu-318 mutant simulating a permanent phospho-Ser-318 modification increased Akt phosphorylation and glucose uptake
Amorim et al., J Thorac Cardiovasc Surg 2010 (Disease Models, Animal...) : However, insulin stimulated glucose uptake was normal in the infarcted hearts, consistent with normal insulin induced phosphorylation of Akt and unchanged mRNA expression of glucose transporter type 4
Serrano-Marco et al., Diabetologia 2012 (Insulin Resistance) : GW501516 prevented IL-6 dependent reduction in insulin stimulated v-akt murine thymoma viral oncogene homologue 1 ( AKT ) phosphorylation and in IRS-1 and IRS-2 protein levels
Rodrigues et al., J Endocrinol 2007 (Body Weight...) : In the present study, we assessed the levels of glucose transporter 4 (GLUT-4), GLUT-1, insulin receptor (IR), IR substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K) and Akt expression, as well as insulin stimulated glucose transport and Akt activity in adipocytes from adult rats previously raised in small litters ( SL )
Wang et al., J Environ Sci (China) 2010 (Inflammation...) : And PCB77 was observed to alter insulin activated Akt signaling by TNFalpha secretion for the first time
de Castro Barbosa et al., Metabolism 2013 : L-NAME treatment suppressed Arg effects on : 1 ) nitrite and c-GMP content ; 2 ) glycogen synthesis and glucose uptake ; 3 ) basal and insulin stimulated p-Akt ( Ser ( 473 ) ), total and p-AMPK-a and ACC, and nNOS expression
Deb et al., J Biol Chem 2004 : In addition, Akt activation by serum and insulin is also inhibited by W-7
Blouin et al., Diabetes 2010 (Insulin Resistance) : Although the PKCzeta mediated negative effect of ceramide on insulin stimulated PKB/Akt was dominant in adipocytes, a ceramide action through PP2A outside CEMs, prevented by OKA, was also unraveled
Schattenberg et al., J Biol Chem 2005 (Fatty Liver...) : In parallel, the effects of insulin on Akt activation, glycogen synthase kinase 3, and FoxO1a phosphorylation, and glucose secretion were all significantly decreased in CYP2E1 overexpressing cells ... In the methionine- and choline-deficient diet mouse model of steatohepatitis with CYP2E1 overexpression, insulin induced IRS-1, IRS-2, and Akt phosphorylation were similarly decreased
Liang et al., Am J Physiol Endocrinol Metab 2009 (Insulin Resistance) : Paradoxically, PGC-1alpha overexpression improved muscle insulin sensitivity, as evidenced by elevated insulin stimulated Akt phosphorylation and peripheral glucose disposal
Panariello et al., J Cell Physiol 2012 (Insulin Resistance) : Insulin stimulated Akt phosphorylation was also reduced by about 40 %
Liu et al., Am J Physiol Endocrinol Metab 2012 (Diabetes Mellitus, Type 2...) : Western blotting showed that d-INS stimulated Akt activation in a more rapid and enhanced fashion in the mouse distal ileum compared with those by h-INS
Vind et al., Diabetologia 2012 (Diabetes Mellitus, Type 2...) : This was associated with impaired insulin stimulated GS and AKT2 activity, deficient dephosphorylation at GS sites 2 + 2a, and reduced Thr308 and Ser473 phosphorylation of AKT
Kang et al., J Exp Biol 2008 : In addition, dietary insulin activated Akt/protein kinase B and extracellular signal regulated kinase ( ERK ) in the mosquito midgut, suggesting that, as observed in Caenorhabditis elegans, the midgut may act as a ` signaling center ' for mosquito aging
Zhang et al., Reproductive biology and endocrinology : RB&E 2011 (Genetic Predisposition to Disease...) : Tribbles 3 (TRB3) affects insulin signalling by inhibiting insulin stimulated Akt phosphorylation and subsequent activation
Corbould , J Endocrinol 2007 (Insulin Resistance...) : In the glucose metabolic pathway of insulin signaling, treatment of cells with T 10 nmol/l did not alter insulin stimulated phosphorylation of insulin receptor substrate-1 or Akt , but insulin stimulated phosphorylation of protein kinase C (PKC) zeta was impaired
Wolfrum et al., Proc Natl Acad Sci U S A 2003 : Here, we show that the activation of phosphatidylinositol 3-kinase-Akt by insulin induces Foxa-2 phosphorylation, nuclear exclusion, and inhibition of Foxa-2 dependent transcriptional activity
Markuns et al., Endocrinology 1999 (Diabetes Mellitus, Experimental) : In all three groups of rats, insulin significantly increased ERK2, RSK2, Akt , and p70S6k activities ... Insulin stimulated Akt activity was also significantly greater in the diabetic animals, but there was no change in protein expression
Jeong et al., Acta Physiol (Oxf) 2010 (Ataxia Telangiectasia) : Ataxia telangiectasia mutated (ATM) reportedly plays a role in insulin stimulated activation of Akt in some cell types but not in others ... In contrast, KU55933 prevented insulin stimulated Akt phosphorylation in C2C12 myotubes ... Furthermore, C2C12 myotubes expressing shRNA against ATM displayed reduced insulin stimulated Akt phosphorylation compared to controls ... KU55933 also decreased insulin stimulated Akt phosphorylation in differentiated RD cells ... These model dependent differences in the role of ATM in insulin action demonstrate a role of ATM in insulin stimulated phosphorylation of Akt ( in C2C12 and RD cells ) but also allow the elucidation of a novel, Akt independent role of ATM ( in L6 myotubes and mouse soleus, at the level of AS160 ) in insulin signalling
Robinson et al., Am J Physiol Endocrinol Metab 2007 (Insulin Resistance) : It does not seem to be required for the development of glucose/insulin induced insulin resistance of glucose transport and Akt activation in 3T3-L1 adipocytes
Greulich et al., J Cell Mol Med 2011 (Cardiovascular Diseases...) : In cardiomyocytes, CM from EAT of HFD fed animals increased SMAD2-phosphorylation, a marker for activin A-signalling, decreased sarcoplasmic-endoplasmic reticulum calcium ATPase 2a expression, and reduced insulin mediated phosphorylation of Akt-Ser473 versus CM from SAT and standard diet fed animals
Jacobshagen et al., Eur J Heart Fail 2008 (Cardiomyopathy, Dilated...) : In rabbit isolated cardiac myocytes celecoxib concentration-dependently ( 10-100 micromol/L ) inhibited the insulin induced increase in phosphorylation of Akt and its downstream targets, GSK-3beta and p70 S6 kinase, by reducing the phosphorylation level of the upstream regulator PTEN
Sánchez-Chávez et al., PloS one 2012 (Diabetes Mellitus, Experimental) : Besides, insulin induced phosphorylation of Akt , an effect also blocked by PI3K inhibition
Agazie et al., Am J Physiol Heart Circ Physiol 2001 (MAP Kinase Signaling System) : In addition, insulin stimulated activation of Akt ( also known as protein kinase B ) ( 10-fold over basal ), whereas ATP had little effect ... However, when ATP and insulin were added in combination, ATP dramatically reduced the insulin stimulated Akt activation ( 2-fold above basal )
Sequea et al., J Gerontol A Biol Sci Med Sci 2012 (Insulin Resistance) : CR versus ad libitum rats had greater insulin stimulated glucose uptake and Akt phosphorylation ( pAkt ) on T308 and S473 for both muscles incubated with insulin
López-Hernández et al., FEBS Lett 1999 : The effect of wortmannin or LY294002 on MAPK and Akt activation by progesterone, insulin or Ras was also analyzed
Xu et al., J Immunol 2012 (Inflammation...) : Our data show that genetic deletion of GPR105 confers protection against HFD induced insulin resistance, with reduced macrophage infiltration and inflammation in liver, and increased insulin stimulated Akt phosphorylation in liver, muscle, and adipose tissue
Kim et al., Diabetes Res Clin Pract 2009 (Glucose Intolerance...) : The insulin stimulated incremental changes in phosphorylated IR-beta, IRS, Akt , and GSK-3 beta and in the membrane associated PKC-zeta protein level were reduced in the IGT group compared with those in the control group ( p < 0.05 )
Matsumoto et al., J Biol Chem 2001 : Inhibition of insulin induced activation of Akt by a kinase-deficient mutant of the epsilon isozyme of protein kinase C ... The potential role of the epsilon isozyme of protein kinase C ( PKC ) in the activation of Akt induced by insulin has now been examined ... Expression of a kinase-deficient mutant of PKCepsilon ( epsilonKD ), but not that of wild-type PKCepsilon or of kinase-deficient mutants of PKCalpha or PKClambda, with the use of adenovirus mediated gene transfer inhibited the phosphorylation and activation of Akt induced by insulin in Chinese hamster ovary cells or L6 myotubes ... These results suggest that epsilonKD inhibits the insulin induced phosphorylation and activation of Akt by interfering with the ability of PDK1 to phosphorylate Akt
Jiang et al., Proc Natl Acad Sci U S A 2003 : These data demonstrate a primary role of Akt2 in insulin signaling, significant functional redundancy of Akt1 and Akt2 isoforms in this pathway, and an absolute requirement of Akt protein kinases for regulation of glucose transport and GSK-3 in cultured adipocytes
González-Rodríguez et al., Aging Cell 2012 (Anoxia...) : Conversely, insulin receptor mediated Akt/Foxo1 signaling was attenuated in these aged control mice
Jin et al., J Clin Invest 2011 (Insulin Resistance) : Overexpression of MKL1 or reduction in G-actin decreased insulin stimulated Akt phosphorylation, whereas reduction of STARS expression increased insulin signaling and glucose uptake
Diaz et al., Obesity (Silver Spring) 2012 (Genetic Predisposition to Disease...) : Skeletal muscle of c-Ski mice exhibit impaired insulin stimulated Akt phosphorylation and glucose uptake
Strowski et al., Endocrinology 2004 (Body Weight...) : Compound-2 enhanced insulin stimulated phosphorylation of IR tyrosine and/or Akt in the liver, skeletal muscle, and white adipose tissue, whereas nTZD potentiated the phosphorylation of IR and Akt in the adipose tissue only
Tang et al., J Biol Chem 2005 (MAP Kinase Signaling System) : Attenuation of PTEN expression by RNAi markedly enhanced insulin stimulated Akt and glycogen synthase kinase 3alpha ( GSK-3alpha ) phosphorylation, as well as deoxyglucose transport in 3T3-L1 adipocytes
George et al., Science 2004 (Diabetes Mellitus...) : Expression of the mutant kinase in cultured cells disrupted insulin signaling to metabolic end points and inhibited the function of coexpressed, wild-type AKT
Hori et al., Diabetes 2002 (Diabetes Mellitus, Type 2...) : Insulin induced Akt activation and PKC-zeta/lambda phosphorylation were restored to the control level, although insulin stimulated PI 3-kinase activation was minimally affected in the skeletal muscle and fat tissue of db/db mice
Altomare et al., Oncogene 1998 : This manuscript is the first to describe Akt2 mRNA expression in the developing mouse and the activation of AKT2 by insulin ... We show that HA-tagged AKT2 is activated in response to insulin stimulation in vitro and that activation of AKT2 is not induced in cells pretreated with wortmannin, an inhibitor of phosphatidylinositol 3-kinase ... These data suggest that Akt2 expression is fundamental to the differentiated state of fat and muscle cells and that activation of AKT2 kinase by insulin is mediated through the phosphatidylinositol 3-kinase signaling pathway
Song et al., Circulation 2007 (Diabetes Mellitus, Experimental...) : Exposure of cultured human umbilical vein endothelial cells to either peroxynitrite ( ONOO- ) or high glucose significantly inhibited both basal and insulin stimulated Akt phosphorylation at Ser473 and Akt activity in parallel with increased apoptosis, phosphorylation, and activity of phosphatase and tensin homologue deleted on chromosome 10 ( PTEN )
Wick et al., J Biol Chem 2001 (MAP Kinase Signaling System) : Insulin receptor mediated p62dok tyrosine phosphorylation at residues 362 and 398 plays distinct roles for binding GTPase activating protein and Nck and is essential for inhibiting insulin stimulated activation of Ras and Akt ... Mutations at Tyr ( 362/398 ) of p62(dok) disrupted the interaction between p62(dok) and GAP and decreased the inhibitory effect of p62(dok) on the insulin stimulated activation of Ras and Akt , but not mitogen activated protein kinase
Pender et al., Metabolism 2005 (Insulin Resistance...) : In these 2 groups, there was no difference in the ability of insulin to induce autophosphorylation of the IR, phosphorylation of the downstream serine kinase Akt/PKB , or stimulation of glucose transport
Bloch-Damti et al., Diabetologia 2006 (Carcinoma, Hepatocellular...) : Protection against oxidation mediated impairment in insulin induced phosphorylation of protein kinase B/Akt and in glycogen synthesis was achieved only by combining salicylic acid and SP600125
Kimura et al., Journal of clinical biochemistry and nutrition 2010 : Insulin dependent phosphorylation or activation of insulin receptor, insulin receptor substrate-1 and -2, phosphatidylinositol 3-kinase, Akt and forkhead in rhabdomyosarcoma were not affected by PQ pre-treatment
Kushiyama et al., J Biol Chem 2005 (Diabetes Mellitus, Experimental...) : In addition, the expression levels of IRS-1 and IRS-2 proteins as well as the degrees of insulin induced phosphatidylinositol 3-kinase and Akt activations were attenuated in RELMbeta transgenic mice
Niswender et al., Diabetes 2003 (Anorexia...) : Here, we report that insulin induces tyrosine phosphorylation of the insulin receptor and IRS-1 and -2, increases binding of activated IRS-1 and -2 to the regulatory subunit of PI3K, and activates protein kinase B/Akt , a downstream target of PI3K
Nazari et al., Biochemistry (Mosc) 2011 : Conversely, cortactin mutants lacking the Src homology 3 (SH3) domain inhibited insulin stimulated formation of actin stress fibers and GLUT4 translocation similar to the actin depolymerizing agent cytochalasin D. Wortmannin, genistein, and a PP1 analog completely blocked insulin induced Akt phosphorylation, formation of actin stress fibers, and GLUT4 translocation indicating the involvement of both PI3-K/Akt and the Src family of kinases ... Knockdown of cortactin by siRNA did not inhibit insulin induced Akt phosphorylation but completely inhibited actin stress fiber formation and glucose uptake
Menghini et al., Circulation 2005 (Arteriosclerosis...) : We show that insulin induces GATA2 phosphorylation on serine 401 in a PI-3K/Akt dependent manner
Bertacca et al., Metabolism 2005 (Hyperinsulinism) : Continually high insulin levels impair Akt phosphorylation and glucose transport in human myoblasts
Aoki et al., Am J Physiol Endocrinol Metab 2009 : Insulin stimulated Akt and phosphatase and tensin homologue deleted on chromosome 10 ( PTEN ) activities in the liver were similar in p85alpha-deficient and wild-type mice
Clodfelder-Miller et al., J Biol Chem 2005 (Body Weight) : Insulin regulates the phosphorylation and activities of Akt and glycogen synthase kinase-3 ( GSK3 ) in peripheral tissues, but in the brain it is less clear how this signaling pathway is regulated in vivo and whether it is affected by diabetes
Bosse et al., Am J Physiol Heart Circ Physiol 2013 (Cardiomegaly...) : After a 10-h fast, insulin stimulation ( 2 U/kg ip ) increased ( P < 0.05 ) phosphorylation of Akt ( Ser473 ) and S6 in heart and gastrocnemius similarly in SHR-C vs. SHR-HF
Gulen et al., Immunity 2012 : Although insulin induced AKT activation is known to phosphorylate and inactivate GSK3a and GSK3ß, we found that GSK3a but not GSK3ß formed a constitutive complex to phosphorylate and suppress AKT activation, showing that a reverse action from GSK to AKT can take place
Fu et al., J Biol Chem 2007 (Insulin Resistance) : NR4A3 hyperexpression also led to an increase in insulin mediated tyrosine phosphorylation of insulin receptor substrate-1 as well as Akt phosphorylation
Tzeng et al., Phytomedicine 2013 (Obesity) : Meanwhile, 6-gingerol diminished the insulin stimulated serine phosphorylation of Akt ( Ser473 ) and GSK3ß ( Ser9 )
Choi et al., Proc Natl Acad Sci U S A 2007 (Insulin Resistance) : These improvements in insulin stimulated glucose metabolism were associated with reduced diacylglycerol content in muscle and liver, decreased PKC activity in muscle and PKCepsilon activity in liver, and increased insulin stimulated Akt2 activity in these tissues
Jiang et al., J Clin Invest 1999 (Insulin Resistance...) : In addition, insulin stimulated serine phosphorylation of Akt , a downstream kinase of PI 3-kinase pathway, was also reduced significantly in isolated microvessels from obese rats compared with the lean rats
Hu et al., Diabetologia 2007 (Adenocarcinoma...) : Treatment of ob/ob mice for 20 days with T33 normalised basal and insulin stimulated glucose uptake and increased phosphorylation of Akt and p38 mitogen activated protein kinase in skeletal muscle
Kotova et al., Cell Mol Biol Incl Cyto Enzymol 2006 : Insulin stimulated Akt phosphorylation was not affected by ouabain
Goetze et al., Biochem Biophys Res Commun 2001 : Insulin induced phosphorylation of Akt downstream of PI3K was inhibited by TNFalpha in a similar pattern
Leiria et al., J Physiol 2013 (Insulin Resistance...) : Phosphoinositide 3-kinase (PI3K) inhibition abolished insulin induced phosphorylation of AKT and eNOS in bladder mucosa ... Insulin stimulated AKT and eNOS phosphorylation in mucosa was also impaired in obese mice
Nishitani et al., Nihon Arukoru Yakubutsu Igakkai Zasshi 2008 : On the other hand, addition of insulin did not decrease the JNK activity, showing that insulin induced Akt activation may rather increase JNK activity ... JNK activation may be suppressed by prolonged active Akt or basal active Akt, rather than peaked activation of Akt induced by insulin stimulation
Raturi et al., Biochim Biophys Acta 2008 (Diabetes Mellitus, Type 2) : Using a fluorescent assay based upon a novel pseudo-substrate of PDI, flow cytometry and immunological techniques, we have demonstrated the presence of PDI on the surface of pMP ( termed msPDI ) and its ability to influence insulin mediated Akt phosphorylation ( Thr308 ) in 3T3-L1 fibroblasts
Genua et al., Vitam Horm 2009 : Inhibition of c-Abl tyrosine kinase by STI571 attenuates the effect of insulin on Akt/GSK-3beta phosphorylation and glycogen synthesis, and at the same time, it enhances the effect of insulin on ERK activation, cell proliferation and migration
Zong et al., J Biol Chem 2009 (Body Weight...) : The reduction in skeletal muscle insulin responsiveness occurred without any change in GLUT4 protein expression levels but was associated with an impairment of the insulin stimulated protein kinase B/Akt serine 473 phosphorylation but not threonine 308
Hresko et al., J Biol Chem 2003 : Immunodepleting cytosolic PDK1 from an in vitro reaction containing plasma membrane and cytosol markedly inhibited insulin stimulated phosphorylation of Akt at the PDK1 site ( Thr-308 ) but had no effect on phosphorylation at the PDK2 site ( Ser-473 )
Palanivel et al., Metabolism 2006 : Neither short-term ( 1 hour ) nor long-term ( 24 hours ) treatment with leptin ( 60 nmol/L ) altered basal or insulin stimulated glucose uptake and oxidation, glycogen synthesis, insulin receptor substrate 1 tyrosine, Akt , or glycogen synthase kinase 3beta phosphorylation
Motley et al., Hypertension 2002 : Lysophosphatidylcholine inhibits insulin induced Akt activation through protein kinase C-alpha in vascular smooth muscle cells ... To better understand the intracellular signaling mechanism that causes the association of insulin resistance and hyperlipidemia with cardiovascular diseases, we specifically looked at the ability of lysophosphatidylcholine ( lysoPC ) to inhibit the Akt activation induced by insulin in cultured rat aortic vascular smooth muscle cells ... LysoPC inhibited the insulin induced phosphorylation of Akt at Ser473, and the inhibition was concentration dependent ... Phorbol 12-myristate 13-acetate ( PMA ), a protein kinase C ( PKC ) activator, inhibited the insulin induced phosphorylation of Akt ... PKC-alpha, but not PKC-beta, is expressed in vascular smooth muscle cells, and overexpression of PKC-alpha, but not PKC-beta or PKC-delta, inhibited insulin induced Akt activation
Meng et al., PloS one 2012 : Nox4 gene silencing had a much greater inhibitory effect on insulin induced AKT activation than ERK1/2 activation, whereas it had little effect on the expression of the phosphatases such as MKP-1 and SHIP
Wu et al., Endocrinology 2004 : To examine whether endogenous glucocorticoids modulate insulin 's effect on Akt signaling in the protein and glycogen synthetic pathways in myocardium, we studied three groups of rats ( n = 12 each ) 4 d after either a bilateral adrenalectomy ( ADX ), ADX with physiological stress dose dexamethasone treatment ( ADX + DEX ), or a sham operation ... Insulin enhanced the phosphorylation of Akt ( P < 0.04 ), 4E-BP1 ( P < 0.002 ), and p70 ( S6K ) ( P < 0.0001 ) in ADX, but not in sham rats ... Dexamethasone restored the levels of 4E-BP1 and p70 ( S6K ) phosphorylation and abrogated the insulin stimulated Akt , 4E-BP1, and p70 ( S6K ) phosphorylation
Gardner et al., Experimental biology and medicine (Maywood, N.J.) 2003 : Pretreatment with H2O2 concentration- and time-dependently inhibited insulin induced Akt phosphorylation with significant inhibition observed at 50 microM for 10 min ... A ROS inducer, diamide, also inhibited insulin induced Akt phosphorylation ... However, pretreatment with a protein kinase C inhibitor, GF109203X ( 2 microM ), for 30 min did not block the inhibitory effects of H2O2 on insulin induced Akt phosphorylation, suggesting that protein kinase C is not involved in the inhibition by H2O2
Wiza et al., Diabetologia 2013 (Insulin Resistance) : PRAS40 knockdown ( PRAS40-KD ) in hSkMC decreased insulin mediated phosphorylation of Akt by 50 % ( p? < ?0.05 ) as well as of the Akt substrates glycogen synthase kinase 3 ( 40 % ) and tuberous sclerosis complex 2 ( 32 % )
Kumar et al., Diabetes 2010 : Loss of rictor in fat cells prevents insulin stimulated phosphorylation of Akt at S473, which, in turn, impairs the phosphorylation of downstream targets such as FoxO3a at T32 and AS160 at T642
Zhong et al., Diabetes Metab 2011 (Diabetes Mellitus, Type 2...) : Compared with cells from non-diabetic subjects, adipocytes from T2DM patients showed signs of insulin resistance, with significantly reduced IRS-1 tyrosine and AKT ( Ser 473 ) phosphorylation levels in response to insulin stimulation ... Introduction of NF-?B decoy molecules significantly inhibited both IL-6 secretion and NF-?B activity, while enhancing insulin stimulated IRS-1 tyrosine and AKT ( Ser473 ) phosphorylation in T2DM adipocytes
Cao et al., Science signaling 2009 : Loss of Galpha ( i1 ) and Galpha ( i3 ) severely impaired the activation of Akt and of p70 S6 kinase and 4E-BP1, downstream targets of mTORC1, in response to EGF, heparin binding EGF-like growth factor, and transforming growth factor alpha, but not insulin , insulin-like growth factor, or platelet derived growth factor
Ragolia et al., J Biol Chem 2003 (Hyperglycemia) : Furthermore, we examined the effect of L-PGDS incubation on insulin stimulated Akt , glycogen synthase kinase-3beta ( GSK-3beta ), and ERK phosphorylation
Liu et al., J Biol Chem 2007 (Insulin Resistance) : Our results show that a prolonged treatment of primary hepatocytes with oleate blunted insulin suppression of hepatic gluconeogenesis, and decreased insulin induced phosphorylation of Akt in a p38 dependent manner ... Reduction of the insulin induced Akt phosphorylation by oleate correlated with activation of p38 ... In the presence of p38 inhibition, prolonged exposure of hepatocytes to oleate failed to reduce insulin stimulated phosphorylation of Akt ... An siRNA against p38alpha prevented oleate suppression of the insulin induced phosphorylation of Akt ... Knocking down the PTEN gene prevented oleate to inhibit insulin activation of Akt and insulin suppression of gluconeogenesis
Xiong et al., Mol Cell Biochem 2012 : Src homology 2-containing inositol 5-phosphatase 2 ( SHIP2 ) has been identified as 5'-inositol phosphatase that hydrolyzes PI ( 3,4,5 ) P ( 3 ) to PI ( 3,4 ) P ( 2 ), which negatively regulates insulin induced Akt signaling in skeletal muscle
Zhu et al., Horm Metab Res 2013 (Insulin Resistance) : Consistently, insulin mediated AKT phosphorylation was increased by NR4A3 hyperexpression and decreased following shRNA NR4A3 suppression ... PGA2 augmented insulin stimulated glucose uptake in C2C12 myocytes and AKT phosphorylation after 12-h treatment, without significant effects on basal transport or basal AKT phosphorylation
Loh et al., Diabetologia 2012 (Diabetes Mellitus, Type 2...) : Insulin activates insulin receptor protein tyrosine kinase and downstream phosphatidylinositol-3-kinase (PI3K)/Akt signalling in muscle to promote glucose uptake ... Blood glucose and insulin levels, insulin and glucose tolerance, and insulin induced muscle insulin receptor activation and downstream PI3K/Akt signalling remained unaltered in chow fed Mck-Cre ; Ptpn2 ( lox/lox ) versus Ptpn2 ( lox/lox ) mice
Uto-Kondo et al., J Nutr 2009 : The current results also revealed that gamma-tocotrienol inhibited the insulin stimulated phosphorylation of Akt but not extracellular signal regulated kinase ( ERK ) 1/2 in the insulin signaling pathway of 3T3-L1 preadipocytes ... Therefore, the results of this study suggest that tocotrienol suppresses insulin induced differentiation and Akt phosphorylation in 3T3-L1 preadipocytes
Krystal et al., Mol Cancer Ther 2002 (Carcinoma, Small Cell...) : Both stem cell factor (SCF) and insulin-like growth factor (IGF)-I , components of prominent small cell lung cancer ( SCLC ) autocrine loops, as well as FCS, can potently activate phosphatidylinositol 3-kinase (PI3K)-Akt signaling, albeit with different kinetics
Chen et al., Diabetes 2006 : Inhibition of PI3K/Akt activity with PI3K inhibitor or by expressing the dominant negative p85 or Akt prevented mercury induced insulin secretion inhibition but not ROS production
Nishita et al., J Biol Chem 2004 : Insulin induced the accumulation of SSH1L and active Akt ( a downstream effector of PI3K ), together with a PI3K product phosphatidylinositol 3,4,5-trisphosphate, onto membrane protrusions
Walz et al., J Biol Chem 2010 : Moreover, depletion of WDFY2 leads to impaired phosphorylation of Akt in response to insulin due to isoform specific reduction of Akt2, but not Akt1, protein levels, and to a marked reduction in the insulin stimulated phosphorylation of numerous Akt substrates
Luo et al., Endocrine 2009 (Carcinoma, Hepatocellular...) : In addition, resistin inhibited the insulin induced phosphorylation of Akt independent of AMPK
Biswas et al., Mol Cell Biochem 2010 (Diabetes Mellitus, Experimental...) : We have isolated mahanine, a carbazole alkaloid, from the leaves of Murraya koenegii that prevented palmitate induced inhibition of insulin stimulated phosphorylation of IRbeta, PI3K, PDK1, and Akt in L6 myotubes
Ceschin et al., J Cell Biochem 2009 : It has been previously demonstrated that insulin increases the cell surface presentation of LRP1 in adipocytes and hepatocytes, which is mediated by the intracellular PI(3)K/Akt signaling activation
Hagiwara et al., J Cell Physiol 2012 (Liver Neoplasms) : Our findings suggest that BCAA supplementation may be useful to suppress liver cancer progression by inhibiting insulin induced PI3K/Akt and subsequent anti-apoptotic pathway, indicating the importance of BCAA supplementation to the obese patients with advanced liver disease
Berniakovich et al., J Biol Chem 2008 (Obesity) : We report that insulin activates the redox enzyme activity of p66 ( Shc ) specifically in adipocytes and that p66 ( Shc ) -generated ROS regulate insulin signaling through multiple mechanisms, including AKT phosphorylation, Foxo localization, and regulation of selected insulin target genes
Oak et al., Am J Physiol Endocrinol Metab 2006 (Fetal Growth Retardation) : Insulin stimulated increases in p-PDK-1 ( P < 0.05 ) and p-Akt ( P < 0.0007 ), with no increase in p-PKCzeta, were seen in both CM/SP and SM/SP groups
Kim et al., Diabetes 2000 (Obesity) : In lean rats, insulin ( 10 U/kg i.v. x 2.5 min ) stimulated Akt1 activity 6.2-, 8.8-, and 4.4-fold and Akt2 activity 5.4-, 9.3-, and 1.8-fold in muscle, liver, and adipose tissue, respectively ... Insulin stimulated Akt2 activity decreased 29 % in muscle and 37 % in liver but increased 24 % in adipose tissue ... Akt1 and Akt2 activations by insulin have a similar time course and are maximal by 2.5 min in adipocytes of both lean and obese rats ... We conclude that 1 ) activation of Akt1 and Akt2 in vivo is much less impaired than activation of PI3K in this insulin-resistant state, and 2 ) the mechanisms for divergent alterations in insulin action on Akt1 and Akt2 activities in tissues of insulin-resistant obese rats involve tissue- and isoform-specific changes in both expression and activation
Sachithanandan et al., Hepatology 2010 (Fatty Liver...) : We isolated hepatocytes from WT and SOCS3 LKO mice and examined the effects of tumor necrosis factor a and insulin on Akt phosphorylation and fatty acid metabolism and lipogenic gene expression
Ballou et al., J Biol Chem 2003 : Transient expression of Galphaq ( Q209L ) in Rat-1 fibroblasts inhibited Akt activation induced by platelet derived growth factor or insulin treatment
Klover et al., Endocrinology 2005 (Inflammation...) : In a direct comparison of hepatic insulin signaling in Lep ( ob ) mice treated with anti-IL-6 vs. IgG treated controls, insulin dependent insulin receptor autophosphorylation and activation of Akt ( pSer473 ) were increased by nearly 50 % with IL-6 depletion
Zygmunt et al., Biochem Biophys Res Commun 2010 : In addition, naringenin did not have a significant effect on basal or insulin stimulated Akt phosphorylation while significantly increased AMPK phosphorylation/activation
Bernal-Mizrachi et al., J Clin Invest 2004 (Body Weight...) : Defective insulin secretion and increased susceptibility to experimental diabetes are induced by reduced Akt activity in pancreatic islet beta cells
Howlett et al., Am J Physiol Endocrinol Metab 2008 : Insulin increased AS160 phosphorylation and 14-3-3 binding capacity and insulin receptor substrate-1 and Akt phosphorylation, but the response to insulin was not enhanced by prior exercise
Koga et al., Proc Natl Acad Sci U S A 2006 : However, Hsp90 inhibition has recently been reported to activate Akt and Erk and potentiate Akt activation induced by insulin-like growth factor 1 and insulin , raising the concern that clinical use of Hsp90 inhibitors might promote tumor progression under certain circumstances
He et al., Ann Oncol 2012 (Breast Neoplasms...) : Human epidermal growth factor receptor ( HER2 ), insulin receptor and IGF-I receptor involve the same PI3K/AKT/mTOR signaling, and different antidiabetic pharmacotherapy may differentially affect this pathway, leading to different prognoses of HER2+ breast cancer
Ng et al., J Biol Chem 2010 (Insulin Resistance) : 3T3-L1 adipocytes were rendered insulin-resistant either with chronic insulin or dexamethasone treatment, but conditional activation of Akt2 stimulated hemagglutinin tagged glucose transporter 4 translocation to the same extent in these insulin-resistant and control cells
Yue et al., Am J Physiol Endocrinol Metab 2010 (Diabetes Mellitus, Type 2...) : Soleus muscles were harvested and homogenized in lysis buffer, and insulin induced Akt phosphorylation was determined by Western blotting ... Soleus lysates had decreased insulin induced Akt phosphorylation
Du et al., Science 2003 (Diabetes Mellitus...) : TRB3 : a tribbles homolog that inhibits Akt/PKB activation by insulin in liver
Focke et al., J Neurobiol 2003 : We found that insulin induces a large increase in the phosphorylation of Akt and can initiate DNA synthesis in avian enteric crest derived cells, but is unable to maintain proliferation over time in culture, measured by BrdU incorporation
Brozinick et al., J Biol Chem 2004 : Although latrunculin B impaired insulin stimulated GLUT4 translocation and glucose transport, activation of phosphatidylinositol 3-kinase and Akt by insulin was not rendered ineffective
Li et al., Braz J Med Biol Res 2009 (Diabetes Mellitus, Experimental) : However, insulin or SCF could activate the phosphorylation of ERK1/2 and AKT in the diabetic cortex
Tanaka et al., Metabolism 2007 (Insulin Resistance) : High-fat diet did not affect glucose transporter 4 content or insulin stimulated Akt phosphorylation
Gauthier et al., Am J Physiol Cell Physiol 2001 (MAP Kinase Signaling System) : To investigate whether human intestinal epithelial cell survival involves distinct control mechanisms depending on the state of differentiation, we analyzed the in vitro effects of insulin , pharmacological inhibitors of Fak, MEK/Erk, and PI3-K/Akt , and integrin ( beta1, beta4 ) -blocking antibodies on the survival of the well established human Caco-2 enterocyte-like and HIEC-6 cryptlike cell models
Mander et al., FEBS Lett 2005 (Insulin Resistance) : Knock-down of LAR induced post-receptor insulin resistance with the insulin induced activation of PKB/Akt and MAP kinases markedly inhibited
Xi et al., Hepatology 2011 (Insulin Resistance) : Liver tissues derived from hCRP treated rats showed reduced insulin stimulated insulin receptor substrate (IRS) tyrosine phosphorylation, IRS/phosphatidylinositol 3-kinase (PI3K) association, and Akt phosphorylation, consistent with hCRP induced impairment of hepatic insulin signaling
Cong et al., Mol Endocrinol 1997 : Overexpression of Akt-WT resulted in significant translocation of GLUT4 to the cell surface even in the absence of insulin
Liu et al., J Biol Chem 2002 : Studies suggested that insulin- or growth factor induced 4E-BP1 phosphorylation is mediated by phosphatidylinositol 3-kinase ( PI3-kinase ) and its downstream protein kinase, Akt ... The PI3-kinase inhibitor, wortmannin, did not block UVB induced 4E-BP1 phosphorylation, but blocked both UVB- and insulin induced activation of PI3-kinase and phosphorylation of Akt
Sopasakis et al., Cell Metab 2010 (Diabetes Mellitus...) : Thus, deletion of p110alpha in liver results in markedly blunted insulin signaling with decreased generation of PIP ( 3 ) and loss of insulin activation of Akt , defects that could not be rescued by overexpression of p110beta
Funai et al., Am J Physiol Endocrinol Metab 2009 (Insulin Resistance) : The results indicated that, in isolated rat epitrochlearis muscle, 1 ) elevated phosphorylation of AS160 ( measured using anti-phospho-Akt substrate, PAS-AS160, and phosphospecific anti-Thr ( 642 ) -AS160, pThr ( 642 ) -AS160 ) consistently tracked with elevated insulin stimulated GT ; 2 ) PAS-TBC1D1 was not different from sedentary values at 3 or 27 h postexercise, when insulin sensitivity was increased ; 3 ) insulin stimulated Akt activity was not increased postexercise in muscles with increased insulin sensitivity ; 4 ) PAS-TBC1D1 was increased immediately postexercise, when insulin independent GT was elevated, and reversed at 3 and 27 h postexercise, when insulin independent GT was also reversed ; and 5 ) there was no significant effect of exercise or insulin on total abundance of AS160, TBC1D1, Akt, or GLUT4 protein with any of the protocols
Lee et al., Hepatology 2011 (Fatty Liver...) : ApoC3Tg mice also manifested severe hepatic insulin resistance assessed by a hyperinsulinemic-euglycemic clamp, which could mostly be attributed to increased hepatic diacylglycerol content, protein kinase C-? activation, and decreased insulin stimulated Akt2 activity
Herr et al., J Physiol 2005 : Insulin stimulated plasma membrane association and activation of Akt2 , aPKC zeta and aPKC lambda in high fat fed rodent skeletal muscle ... However, it has yet to be determined in skeletal muscle whether : ( 1 ) insulin increases PM-associated Akt2 , aPKC zeta and/or lambda protein concentration, ( 2 ) the activity of these kinases is altered by insulin at the PM, and ( 3 ) high fat feeding alters the insulin stimulated PM concentration and/or activity of Akt2 and aPKC zeta/lambda ... In normal skeletal muscle, total PI3-kinase, Akt2 and aPKC zeta/lambda activities were increased by insulin ... PM-associated aPKC zeta and lambda, and aPKC zeta/lambda activity, but not Akt2 or Akt2 activity, were increased by insulin in normal muscle ... Insulin stimulated total PI3-kinase, Akt2 and aPKC zeta/lambda activities were reduced in the high fat fed animals ... In addition, high fat feeding impairs insulin stimulated activation of total aPKC zeta/lambda and Akt2 , as well as PM association and activation of aPKC zeta and lambda
Kim et al., J Neural Transm 2005 (Nerve Degeneration) : Insulin stimulated protein kinase B ( Akt ) activity, whereas AMPA pretreatment did not alter the insulin stimulated Akt activity
Ou et al., Mol Cell 2011 (Cell Transformation, Neoplastic...) : In cells lacking TBK1, insulin activates AKT normally, but AKT activation by exocyst dependent mechanisms is impaired
Ito et al., J Lipid Res 2011 (Obesity) : The Akt inhibitor API-2 and the c-Jun N-terminal kinase (JNK) inhibitor SP600125 selectively inhibited insulin regulation of CIDEA and CIDEC expression, respectively, whereas the MAPK/ERK kinase inhibitor U0126 and the p38 inhibitor SB203580 did not ... Furthermore, insulin increased both Akt and JNK phosphorylation, which was abrogated by the PI3K inhibitors
Liu et al., Am J Physiol Endocrinol Metab 2009 (Insulin Resistance) : Suppressing Grb2 expression in C ( 2 ) C ( 12 ) myoblasts enhances insulin stimulated insulin receptor substrate (IRS)-1, tyrosine phosphorylation, and Akt phosphorylation, which is associated with decreased IRS-1 serine phosphorylation at residues 307, 612, and 636/639
Florholmen et al., Diabetologia 2006 (Insulin Resistance) : In line with these observations, chronic LIF treatment reduced insulin mediated phosphorylation of both Akt/protein kinase B (PKB) and glycogen synthase kinase ( GSK ) -3 ... Chronic LIF treatment induced insulin resistance, possibly mediated by altered expression of Socs3 and Slc2a4, and impaired insulin mediated phosphorylation of GSK-3 and Akt/PKB
Motley et al., Hypertension 2003 : Insulin induced Akt activation is inhibited by angiotensin II in the vasculature through protein kinase C-alpha ... By immunoblotting with a phospho-specific antibody for Akt, we found that Ang II inhibits insulin induced Akt phosphorylation in a time- and concentration dependent manner ... A protein kinase C ( PKC ) activator, phorbol 12-myristate 13-acetate, also inhibited insulin induced Akt phosphorylation ... Moreover, overexpression of PKC-alpha but not PKC-beta isoform by adenovirus inhibited insulin induced Akt phosphorylation
Koch et al., Br J Nutr 2013 (Glucose Intolerance) : Quercetin was found to inhibit basal and insulin induced phosphorylation of Akt ( Ser473 ), a downstream target of PI3K, in HT-22 cells, whereas naringenin and curcumin had no effect ... In Djungarian hamsters ( Phodopus sungorus ) naringenin and quercetin ( 10 mg/kg administered orally ) diminished insulin induced phosphorylation of Akt ( Ser473 ) in the arcuate nucleus, indicating a reduction in hypothalamic PI3K activity
Ceresa et al., Mol Cell Biol 1998 : Although there was an approximately 50 % decrease in the insulin stimulated activation of the phosphatidylinositol 3-kinase associated with IRS1, insulin stimulated Akt kinase phosphorylation and activation were unaffected
Huang et al., J Biol Chem 2005 : Insulin induced Akt1 and Akt2 phosphorylation was reduced in myotubes treated with siIRS-1, but only Akt2 phosphorylation was reduced in myotubes treated with siIRS-2
Zhang et al., Free Radic Biol Med 2009 : Insulin signaling to mTORC1 is dependent upon phosphorylation of Akt/PKB and the inhibition of the tuberous sclerosis complex ( TSC1/2 ), thereby enhancing the phosphorylation of 4E-BP1 and S6K1
Park et al., J Biol Chem 2005 (Insulin Resistance) : Moreover, insulin stimulated phosphorylation of IRS-1 and Akt2/protein kinase B were drastically reduced in the depleted cells ... Taken together, our data suggest that PM GLUT4 content and insulin signal pathway intermediates are modulated by the alteration of cellular mtDNA content, and the reductions in the expression of IRS-1 and insulin stimulated phosphorylation of IRS-1 and Akt2/protein kinase B are associated with insulin resistance in the mtDNA depleted L6 GLUT4myc myocytes
Tsai et al., Endocrinology 2003 (Carcinoma, Hepatocellular...) : The activity of FOXO proteins is principally regulated by activation of protein kinase B (PKB)/Akt by insulin and other cytokines
Ismail et al., J Cell Biochem 2013 (Insulin Resistance) : Nelfinavir also inhibited phosphorylation of Map/ERK kinase without affecting insulin stimulated Akt phosphorylation
Kralik et al., Endocrinology 2002 : Insulin , but not hyperosmolarity, clearly increased the activities of PI3K and Akt
Kim et al., Antioxid Redox Signal 2011 (Insulin Resistance) : Inhibition of the phosphatidylinositol 3-kinase (PI3-K) pathway during insulin pretreatment restored acute insulin mediated Akt phosphorylation
Kim et al., Biogerontology 2008 : Insulin induced PI3K/Akt activation is known to inhibit a family of Forkhead transcription factors ( FOXO ), which can lead to increased oxidative stress in several model organisms
Hayakawa et al., Endocrinology 2002 : PrRP and insulin rapidly and transiently stimulated the activation of Akt, and the PI3K inhibitor wortmannin blocked the PrRP- or insulin induced activation of Akt
Skurk et al., Horm Metab Res 2009 (Inflammation...) : Effect of conditioned media from mature human adipocytes on insulin stimulated Akt/PKB phosphorylation in human skeletal muscle cells : role of BMI and fat cell size ... The aim of this study was to investigate if adipocyte conditioned media interfere with insulin stimulated Akt/PKB phosphorylation in in vitro differentiated human skeletal muscle cells ... Insulin induced phosphorylation of the signaling proteins Akt/PKB and ERK-2 was analyzed using a bead based fluorescence detection system and was correlated to BMI and fat cell size ... Adipocyte conditioned media reduced insulin stimulated Akt/PKB phosphorylation in a manner depending on BMI and fat cell volume ... These data provide first direct evidence that secreted factors from freshly isolated mature fat cells separated according fat cell size reduce insulin stimulated Akt/PKB phosphorylation in human skeletal muscle cells and may contribute to the pathogenesis of obesity associated insulin resistance
Wan et al., J Endocrinol Invest 2009 (Insulin Resistance) : In accordance with the reduced IRS-2 level, the insulin stimulated phosphorylation of Akt was diminished in the PA-treated cells
Asano et al., Biol Pharm Bull 2007 (Diabetes Mellitus...) : Thus, the drugs which restore the impaired insulin induced PI 3-kinase/AKT activation, for example, by suppressing JNK or p70S6K, PTEN or SHIP2, could be novel agents to treat diabetes mellitus
Karlsson et al., Diabetes 2006 (Diabetes Mellitus, Type 2) : Insulin increased phosphorylation of Akt and Akt substrate of 160 kDa (AS160) in a dose dependent manner, with comparable responses between groups
Fiorentino et al., Hepatology 2010 (Fatty Liver...) : TACE overexpression significantly impaired insulin dependent phosphorylation of AKT , GSK3, and FoxO1 in mouse hepatocytes
Shinoda et al., J Cell Biochem 2006 : In the presence of insulin , however, this suppression was blunted, and adiponectin enhanced the insulin induced phosphorylations of the main downstream molecule insulin receptor substrate-1 and Akt
Sasaoka et al., Diabetologia 2001 : Although PI ( 3,4,5 ) P3 and PI ( 3,4 ) P2 are known to possibly activate a downstream molecule of PI3-kinase Akt in vitro, overexpression of WT-SHIP2 inhibited insulin induced phosphorylation and activation of Akt ... Our results indicate that SHIP2 plays a negative regulatory role via the 5'-phosphatase activity in insulin signalling, and that PI ( 3,4,5 ) P3 rather than PI ( 3,4 ) P2 is important for in vivo regulation of insulin induced Akt activation leading to glycogen synthesis in L6 myotubes
Sugita et al., Mol Cancer Res 2010 (Neoplasm Invasiveness...) : NO donor inhibited insulin/IGF-I stimulated phosphorylation of insulin receptor/IGF-I receptor, IRS-1, Akt/PKB , and glycogen synthase kinase-3beta along with decreased expression of IRS-1 protein in MIAPaCa-2 cells, whereas NO donor enhanced the phosphorylation of extracellular signal regulated kinase-1/2
He et al., Mol Endocrinol 2007 (Diabetes Mellitus) : In this paper, we demonstrate that Akt is not the direct target gene of miR-29 and that the negative effects of miR-29 on insulin signaling might be mediated by other unknown intermediates
Guillermet-Guibert et al., Proc Natl Acad Sci U S A 2008 : In fibroblasts, which express p110beta but not p110gamma, p110beta mediated Akt activation by the GPCR ligands stromal cell derived factor, sphingosine-1-phosphate, and lysophosphatidic acid but not by the Tyr kinase ligands PDGF, insulin , and insulin-like growth factor 1
Moreno et al., FASEB J 2011 (Insulin Resistance) : T2 increased insulin stimulated Akt phosphorylation levels ( ~2.5-fold ; P < 0.05 vs. HFD )
Bakker et al., Diabetes 2008 : Analysis of intracellular signaling in muscle resistance arteries showed that PKC theta activation reduced insulin mediated Akt phosphorylation ( Ser ( 473 ) ) and increased extracellular signal related kinase ( ERK ) 1/2 phosphorylation ... Inhibition of PKC theta restored insulin mediated vasoreactivity and insulin mediated activation of Akt and ERK1/2 in the presence of PA
Chabowski et al., Acta Physiol (Oxf) 2013 (Insulin Resistance) : Both PA and OA fatty acids induced the protein expression of FAT/CD36 and FATP-2 with concomitant : ( i ) reduction in GLUT-2 protein content, ( ii ) inhibition of insulin stimulated glucose uptake, ( iii ) reduction in insulin stimulated activation of AKT and GSK, ( iv ) accumulation of either DG ( PA and OA ) or ceramide ( only PA )
Hagan et al., Mol Cell Biol 2008 : Insulin signaling through phosphatidylinositol 3-kinase ( PI 3-kinase ) activates the protein kinase Akt through phosphorylation of its threonine 308 and serine 473 residues by the PDK1 protein kinase and the Rictor-mammalian target of rapamycin complex ( mTORC2 ), respectively
Lu et al., J Biol Chem 2013 (Insulin Resistance) : In line with the in vivo results, insulin induced AKT and FoxO1 phosphorylation were potentiated by inhibition of Sirt1 in a cultured hypothalamic cell line
Lee et al., Am J Physiol Cell Physiol 2009 (Diabetes Mellitus, Type 2...) : Previously, we showed the phosphorylation of myosin bound phosphatase substrate MYPT1, a marker of the vascular smooth muscle cell ( VSMC ) contraction, was negatively regulated by Akt ( protein kinase B ) phosphorylation in response to insulin stimulation ... GK VSMCs had impaired basal and insulin induced Akt phosphorylation as well as increases in basal MYPT1 phosphorylation, inducible nitric oxide synthase (iNOS) expression, and nitrite/nitrate production compared with Wistar-Kyoto controls
Wong et al., Biotechnol Bioeng 2006 : The phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin, totally blocked the effect of both zinc and insulin on Akt activation, indicating the involvement of PI3K in the activation of Akt by zinc, rather than zinc acting on Akt directly
Tsuchiya et al., Endocrinology 2007 (Inflammation...) : Insulin stimulated tyrosine phosphorylation of insulin receptor substrate-1 and serine phosphorylation of Akt/Akt2 in soleus muscle was markedly impaired in HFD fed mice but reversed by L-NAME treatment
Zheng et al., J Am Soc Nephrol 2005 (Insulin Resistance) : Similarly, insulin induced Akt phosphorylation was preserved in IRS1-/- mice but was markedly attenuated in IRS2-/- mice
Hiromura et al., Kidney Int 2002 : Akt was activated by insulin and IGF-I during apoptosis ... Our results also showed that the CDK-inhibitor p21 was increased by insulin and that p21 up-regulation was PI3-kinase/Akt pathway dependent
Kagawa et al., Endocrinology 2008 (Body Weight) : Insulin induced phosphorylation of Akt was decreased in the SHIP2 overexpressing fat, skeletal muscle, and liver
Frøsig et al., J Physiol 2007 (Hyperinsulinism) : Insulin increased ( P < 0.05 ) both insulin receptor substrate (IRS)-1 and IRS-2 associated phosphatidylinositol (PI)-3 kinase activity and led to increased ( P < 0.001 ) phosphorylation of Akt on Ser ( 473 ) and Thr ( 308 ) in skeletal muscle
Davis et al., Diabetes 2010 (Diabetes Mellitus, Type 2...) : Hepatic insulin receptor substrate (IRS)-1 and IRS-2 expression and insulin stimulated Akt-phosphorylation are decreased in BKS-db primary hepatocytes
Cardoso et al., Life Sci 2005 : Insulin induced IR, IRS-1 and IRS-2 tyrosine phosphorylation, association of these substrates with PI 3-kinase and Akt and ERK phosphorylation were similar in the three groups of animals in both tissues
Walker et al., Biochem J 1998 : Stimulation of rat adipocytes or rat hepatocytes with insulin induced the activation of PKBalpha and PKBbeta with similar kinetics ... Insulin induced the activation of PKBalpha in rat skeletal muscle in vivo, with little activation of PKBbeta
Miegueu et al., Am J Physiol Gastrointest Liver Physiol 2013 : These SP effects were accompanied by downregulation of insulin receptor substrate 1 ( -82 ± 2 %, P < 0.01 ) and GLUT4 ( -76 ± 2 %, P < 0.01 ) mRNA expression, and SP acutely blocked insulin mediated stimulation of fatty acid uptake and Akt phosphorylation
Shao et al., J Endocrinol 2000 (Diabetes Mellitus, Experimental...) : Insulin increased Akt-Ser ( 473 ) phosphorylation by two- to fivefold in muscle and adipose tissue from all mice ... These data implicate decreased insulin stimulated Akt kinase activity as an important component underlying impaired GLUT4 translocation and insulin resistance in tissues from db/db mice
Kuoppamaa et al., Diabetes Metab Res Rev 2008 (Diabetes Mellitus, Type 2) : Insulin stimulated phosphorylation of Akt-Ser ( 473 ) or Akt-Thr ( 308 ) was comparable in type 2 diabetic and non-diabetic muscles, and unaltered by the addition of globular adiponectin in either group
Sun et al., J Biol Chem 2012 (Diabetes Mellitus, Type 2...) : Consequently, MARK4 deficiency mitigated insulin resistance associated with diet induced obesity by dramatically enhancing insulin stimulated AKT phosphorylation in major metabolic tissues
Sartori et al., Endocrinology 2009 (Insulin Resistance) : This was due, at least in part, to the improvement of insulin signal transduction in the vasculature, as evidenced by increased insulin induced phosphorylation of Akt and endoethelial nitric oxide synthase in aortas harvested from melatonin treated high-fat diet fed mice
Engberding et al., Arterioscler Thromb Vasc Biol 2009 (Diabetes Mellitus, Type 2...) : IGF1R overexpression in VSMCs impaired insulin induced Akt phosphorylation ... Conversely, IGF1R downregulation by siRNA allowed assembly of insulin holoreceptors, enhanced insulin induced phosphorylation of its receptor, Akt , Erk1/2, and further augmented insulin induced glucose uptake
Valverde et al., FEBS Lett 2000 : However, activation of Akt/PKB or p70 S6 kinase ( p70 ( s6k ) ) by insulin remained unaltered
Prudente et al., Diabetes 2005 (Cardiovascular Diseases...) : As compared with control HepG2 cells, insulin induced Ser473-Akt phosphorylation was reduced by 22 % in Q84- ( P < 0.05 vs. control cells ) and by 45 % in R84 transfected cells ( P < 0.05 vs. Q84 transfected and P < 0.01 vs. control cells )
Conejo et al., J Cell Physiol 2001 (MAP Kinase Signaling System) : Insulin stimulated IRS-1 association with p85alpha leading to the activation of PI3-kinase, and, subsequently AKT and p70S6-kinases
Deshmukh et al., Cell Mol Life Sci 2009 : Leucine also reduced insulin stimulated Akt phosphorylation, glucose uptake and glucose incorporation to glycogen ( 39 %, 39 % and 37 %, respectively ), and this reduction was restored after S6K1 silencing
Nakamura et al., J Biol Chem 2001 : These results suggest that the excessive glucose flux through the HBP may direct retinal neurons to undergo apoptosis in a bimodal fashion ; i.e. via perturbation of the neuroprotective effect of insulin mediated by Akt and via induction of apoptosis possibly by altered glycosylation of proteins
Laviola et al., Diabetes 2001 (Diabetes Mellitus, Experimental) : Insulin induced phosphorylation of Akt on Thr-308 was increased fivefold in diabetic heart, whereas Akt phosphorylation on Ser-473 was normal
Nielsen et al., Am J Physiol Endocrinol Metab 2002 (Glycogen Storage Disease Type V...) : The insulin stimulated increase in Akt phosphorylation was smaller in the McArdle patients than in controls ( 45 +/- 13 vs. 76 +/- 13 %, P < 0.05, respectively ), whereas basal and insulin stimulated glycogen synthase kinase 3alpha and protein phosphatase-1 activities were similar in the two groups
Sanderson et al., Neurol Res 2009 (Brain Ischemia...) : Insulin induced Akt phosphorylation was suppressed by the PI3K inhibitor wortmannin ... Insulin induces robust PI3K dependent phosphorylation of Akt by 30 minute reperfusion and results in improvement of hippocampal structure and function
Ijuin et al., Mol Cell Biol 2008 (Body Weight...) : Furthermore, in vitro knockdown studies in L6 myoblast cells revealed that reduction of SKIP expression level increased insulin stimulated Akt/PKB phosphorylation and 2-deoxyglucose uptake
Lu et al., J Biol Chem 2013 (Insulin Resistance...) : In MacGHR KO AT, crown-like-structures were increased with decreased insulin dependent Akt phosphorylation
Storz et al., Eur J Biochem 1999 (Diabetes Mellitus, Type 2...) : Cross-talk mechanisms in the development of insulin resistance of skeletal muscle cells palmitate rather than tumour necrosis factor inhibits insulin dependent protein kinase B (PKB)/Akt stimulation and glucose uptake
Hong et al., PLoS Genet 2012 : Conversely, AKT mediated insulin signaling suppressed FOXO mediated sNPF/NPY expression, which resulted in decreasing food intake
Carvalho-Filho et al., Am J Physiol Endocrinol Metab 2006 (Insulin Resistance) : In this study, we observed that LPS induced insulin resistance in the muscle of wild-type mice, as demonstrated by reduced insulin induced tyrosine phosphorylation of IRbeta and IRS-1, reduced IRS-1 expression and reduced insulin induced serine phosphorylation of Akt
Low Wang et al., J Diabetes Complications 2013 (Disease Models, Animal...) : With insulin stimulation, Akt phosphorylation increased in STD, but not HFHS
Kim et al., Endocrinology 2011 (Hyperinsulinism...) : More importantly, acute insulin stimulation after chronic insulin treatment resulted in blunted phosphorylation of Akt , p70S6K, and glycogen synthase kinase-3ß ... Insulin induced Akt phosphorylation was lower in dorsal root ganglion neurons from BKS-db/db compared with control BKS-db+ mice
Sakaue et al., J Biol Chem 2003 (MAP Kinase Signaling System) : In Cre expressing PDK-1 ( lox/lox ) adipocytes in which the abundance of PDK-1 was reduced by approximately 85 %, the insulin induced phosphorylation both of Akt on threonine 308 and of p70 S6 kinase on threonine-389 was markedly inhibited
Park et al., Diabetes Res Clin Pract 2007 (Insulin Resistance) : Interestingly, the expression of IRS-1 associated with insulin signaling was decreased by 90 % in the depleted cells, and the insulin stimulated phosphorylation of IRS-1 and Akt2/PKB were drastically reduced in the depleted cells ... Taken together, our data suggest that PM GLUT4 content and insulin signal pathway intermediates are modulated by the alteration of cellular mtDNA content, and the reduction in the expression of IRS-1 and insulin stimulated phosphorylation of IRS-1 and Akt2/PKB are associated with insulin resistance in the mtDNA depleted L6 GLUT4myc myocytes
Nakata et al., Biochem Biophys Res Commun 2007 (Insulin Resistance) : In addition, resistin inhibited insulin induced phosphorylation of Akt in islets as well as other insulin target organs
Gridley et al., Cell Signal 2006 (Tuberous Sclerosis) : The knockdown of AS250 had no effect on insulin activation of the kinases, Akt , 70 kDa S6 kinase, or ERK1/2, or on insulin stimulated actin bundling, and it had only a slight effect on insulin stimulated GLUT4 translocation
Lee et al., Am J Physiol Endocrinol Metab 2012 (Diabetes Mellitus, Type 2...) : Concurrently, insulin mediated Akt phosphorylation also increased after INT131 treatment in DIO mice
Laviola et al., Diabetes 2006 : Insulin induced phosphorylation of Akt also occurred to a greater extent and earlier in omental than in subcutaneous fat ( P < 0.05 ) in the absence of significant changes in Akt protein content
Thirone et al., Diabetes 2006 (Insulin Resistance) : Opposite effect of JAK2 on insulin dependent activation of mitogen activated protein kinases and Akt in muscle cells : possible target to ameliorate insulin resistance ... Conversely, insulin stimulated Akt phosphorylation, glucose uptake, and GLUT4 translocation were not affected by siJAK2
Zhang et al., Cardiovasc Res 2007 : The improved cardiac response was accompanied by facilitated insulin stimulated glucose uptake, GLUT4 translocation and upregulation of Akt and eNOS expression ( p < 0.01 ) ... Moreover, pretreatment with either LY294002, a phosphatidylinositol-3 kinase (PI-3K) inhibitor or L-NAME, a NOS inhibitor, abolished the exercise induced sensitization of myocardial contractile response to insulin, insulin induced NO production and phosphorylation of Akt and eNOS
Dennis et al., J Biol Chem 2011 : At fasting ( 1x ) or 2x ( 2xAA ) concentrations of amino acids, insulin maximally stimulated Akt phosphorylation but had no effect on global rates of protein synthesis
Bradley et al., Am J Physiol Endocrinol Metab 2007 : Insulin ( 10 and 20 mU.min-1.kg-1 ) increased FBF, MXD, GIR, Rd, and HLGU as well as liver, muscle, and aorta P-Akt/Akt and decreased Ra ( all P < 0.05 )
Meares et al., FEBS Lett 2004 : Inhibition of Hsp90 with geldanamycin amplified Akt phosphorylation induced by insulin-like growth factor-1 (IGF-1) or insulin, indicating that Hsp90 normally buffers these signals
Angin et al., Biochem J 2012 (Calcium Signaling...) : Under both culture conditions, insulin stimulated glucose uptake and Akt phosphorylation were abrogated or markedly reduced
Schütt et al., J Endocrinol 2004 : The impaired insulin secretion by ritonavir, nelfinavir and saquinavir was associated with decreased insulin stimulated IRS-2 phosphorylation, and, for nelfinavir and saquinavir, with decreased insulin stimulated IRS-1 and Thr308-Akt phosphorylation
Lee et al., J Biol Chem 2009 (Diabetes Mellitus, Type 2...) : Insulin induced phosphorylation of Akt , AS160, S6K, and S6 was also decreased in skeletal muscle
Greene et al., Biochem Biophys Res Commun 2006 : The 3A mutant abrogated the inhibitory effect of PKCdelta on insulin stimulated IRS-1 Tyr phosphorylation, while reductions in insulin stimulated IRS-1 Tyr phosphorylation, cellular proliferation, and Akt activation were observed with the 3E mutant
Ciaraldi et al., Diabetes 2002 (Diabetes Mellitus, Type 2) : Insulin stimulated serine phosphorylation of Akt was augmented after troglitazone ( 170 +/- 34 % of pre-Rx response, P < 0.05 ) treatment and unchanged by metformin
Lee et al., Mol Biol Cell 2009 (Alzheimer Disease) : In cell culture, Abeta ( i ) expression inhibited both insulin induced Akt phosphorylation and activity
van den Brom et al., Cardiovascular diabetology 2010 (Cardiomyopathies...) : Finally, reduced RV insulin stimulated phosphorylation of Akt was found in ZDF vs. ZL ( p < 0.05 )
Duarte et al., Biochim Biophys Acta 2008 : Thus, insulin mediated activation of IR/IGF-1R stimulates PI-3K/Akt and inhibits GSK-3beta signaling pathways, modifying neuronal antioxidant defense-, glucose metabolism- and anti-apoptotic associated protein synthesis
Miao et al., Inflamm Res 2012 (Insulin Resistance) : We identified two different but physiologically relevant IR models characterized by attenuated insulin induced phosphorylation of insulin receptor substrate-1 and AKT in TNF-a- or DEX treated HepG2 cells
Matsushima et al., J Biol Chem 2006 : Akt was activated by insulin alone in the C57BL/6 strain and but not in db/db mice
Protzek et al., Comp Biochem Physiol A Mol Integr Physiol 2010 : The insulin induced Akt phosphorylation was more pronounced in the pectoral muscle, compared to liver
Di Paolo et al., J Am Soc Nephrol 2006 (Diabetes Mellitus...) : In view of the critical role of AKT in insulin signaling and tumorigenesis, the in vivo expression and activation of this kinase and of IRS-1 and IRS-2 were explored in PBMC of 30 patients who were treated long term with rapamycin ... A marked decrease of basal and insulin stimulated AKT phosphorylation, which correlated with the increase of patients ' insulin resistance, and a significant increase of IRS total protein expression, together with a lower ( IRS-2 ) or absent ( IRS-1 ) increase of insulin induced tyrosine phosphorylation, were found
Lin et al., J Cell Physiol 2011 : The purpose of this study was to test a hypothesis that T3 promotes glucose uptake via enhancing insulin induced Akt phosphorylation and VAMP2 translocation in 3T3-L1 adipocytes ... T3 significantly enhanced insulin induced phosphorylation of Akt , cytoplasma to cell membrane translocations of vesicle associated membrane protein 2 ( VAMP2 ) and glucose transporter 4 (GLUT4), and glucose uptake in adipocytes
Ueda et al., Food Funct 2010 : Cg and EGCg decreased phosphorylation of PKC?/? in the presence of insulin without affecting insulin induced phosphorylation of IR, and Akt
Liu et al., Sheng Li Xue Bao 2007 : Moreover, insulin resulted in 1.7-fold and 1.5-fold increases in Akt and JNK phosphorylation in I/R myocardium, respectively ( n=6, P < 0.05 ) ... These results demonstrate that insulin simultaneously activates both Akt and JNK, and the latter further increases the phosphorylation of Akt which attenuates MI/R injury and improves heart function ; this cross-talk between Akt and JNK in the insulin signaling is involved in insulin induced cardioprotective effect
Andrade et al., Mol Endocrinol 2013 : GnRH also stimulated c-Jun N-terminal kinase (JNK) and ERK activation, whereas insulin alone stimulated Akt
Foukas et al., EMBO Mol Med 2013 (Metabolic Diseases) : This beneficial effect of p110a inactivation derives in part from a suppressed down-regulation of insulin receptor substrate (IRS) protein levels induced by age related hyperinsulinemia, and correlates with enhanced insulin induced Akt signalling in aged p110a-deficient mice
Salvadó et al., Diabetologia 2013 : Moreover, the ability of oleate to prevent palmitate induced ER stress and inflammation ( nuclear factor-kappa B [ NF-?B ] DNA binding activity and expression and secretion of IL6 ) as well as insulin stimulated Akt phosphorylation and 2-deoxyglucose uptake was reversed in the presence of the AMPK inhibitor compound C or by overexpression of a dominant negative AMPK construct
Gosmanov et al., Am J Physiol Regul Integr Comp Physiol 2003 : Glucose, but not mannitol, impaired insulin stimulated phosphorylation of Akt and p38 MAPK in the plantaris and soleus muscles, respectively
Ciaraldi et al., Endocrinology 2007 (Insulin Resistance) : However, GSK3alpha overexpression impaired insulin action on pS473-Akt
Ross et al., Biochem Biophys Res Commun 2000 (Insulin Resistance) : Insulin stimulated phosphorylation of Akt on Ser ( 473 ) was not impaired in insulin-resistant cells
Soloff et al., Mol Hum Reprod 2004 : We were unable to detect any significant differences between primary and immortalized cells in signal pathways such as epidermal growth factor stimulated epidermal growth factor receptor phosphorylation, insulin stimulated Akt phosphorylation, oxytocin and lysophosphatidic acid stimulated extracellular signal regulated kinase 1 and 2 phosphorylation, myosin light chain phosphorylation, and interleukin-1 induction of IkappaBalpha degradation
Liu et al., Biochem J 2009 (Diabetes Mellitus, Type 2...) : Treatment with palmitate increased IRS1 serine phosphorylation and reduced insulin stimulated Akt phosphorylation and GLUT4 translocation, indicating insulin resistance
Kondapaka et al., Clin Cancer Res 2004 : UCN-01 also inhibits insulin induced Thr308 but not Ser473 phosphorylation of Akt associated with the plasma membranes and low-density microsomes and inhibits translocation of GLUT4 from low-density microsomes to plasma membranes as expected from the glucose transport activity measurements ... These data suggest that UCN-01 induces clinical insulin resistance by blocking Akt activation and subsequent GLUT4 translocation in response to insulin , and this effect appears to occur by inhibiting Thr308 phosphorylation even in the face of almost completely unaffected Ser473 phosphorylation
Yoshiga et al., Mol Endocrinol 2007 : Insulin induced Akt activation and the phosphorylation of forkhead transcription factor ( FKHR/Foxo1 ), a negative regulator of PPARgamma transcription, were up-regulated by SH2-B overexpression, but reduced in SH2-B-deficient MEFs
Speed et al., ACS chemical neuroscience 2010 : Since Akt2 activation is mediated by insulin , these data further implicate insulin signaling as an important modulator of DAT function and dopaminergic tone
Duplain et al., J Physiol 2008 (Insulin Resistance) : Moreover, FeTPPS restored insulin stimulated Akt phosphorylation and insulin stimulated glucose uptake in isolated skeletal muscle in vitro
Huang et al., PloS one 2009 (Diabetes Mellitus, Type 2...) : Among the novel hits was PALD ( KIAA1274, paladin ), a previously uncharacterized protein that when overexpressed led to inhibition of insulin 's ability to down regulate a FOXO1A-driven reporter gene, reduced upstream insulin stimulated AKT phosphorylation, and decreased insulin receptor (IR) abundance ... Conversely, knockdown of PALD gene expression resulted in increased IR abundance, enhanced insulin stimulated AKT phosphorylation, and an improvement in insulin 's ability to suppress FOXO1A-driven reporter gene activity
Marinho et al., J Cell Physiol 2012 (Diabetes Mellitus, Type 2...) : Here, we demonstrated that chronic exercise increased the basal levels and insulin induced Akt serine phosphorylation in the liver of diet induced obese mice
Huynh et al., Diabetes 2010 (Diabetes Mellitus, Type 2...) : Consistent with increased insulin sensitivity, mice with ablated hepatic leptin signaling had increased insulin stimulated phosphorylation of Akt in the liver
Meléndez et al., J Cell Biochem 2000 : They also suggest that AKT , a PI 3-kinase downstream effector molecule, could mediate insulin stimulation of g33 mRNA
Bhandari et al., Kidney Int 2001 : Insulin also activated Akt that lies downstream of PI 3-kinase
Rojas et al., Endocrine 2003 (Disease Models, Animal...) : In parallel, insulin induced Akt phosphorylation was reduced in both tissues of epinephrine treated rats, and in liver but not in muscle of dexamethasonetreated rats ... The reduction in insulin induced Akt phosphorylation may help to explain the insulin resistance in liver and muscle of epinephrine treated rats and in the liver of dexamethasone treated rats
Oita et al., Pflugers Arch 2010 (MAP Kinase Signaling System) : In differentiated C2C12 myoblasts, visfatin had no effects on insulin stimulated Akt phosphorylation nor on activation of the Akt signalling pathway
Liu et al., Am J Physiol Endocrinol Metab 2010 (Diabetes Mellitus, Type 2...) : Tribbles homolog 3 (TRIB3) was found to inhibit insulin stimulated Akt phosphorylation and modulate gluconeogenesis in rodent liver
Schulman et al., Am J Physiol Heart Circ Physiol 2007 (Insulin Resistance) : Insulin increased aortic serine phosphorylation of Akt in 3-mo rats by 120 % over 24-mo rats ( P < 0.05 ) and serine phosphorylation of endothelial NO synthase (eNOS) in 3-mo rats by 380 % over 24-mo rats ( P < 0.05 )
Ni et al., Proc Natl Acad Sci U S A 2007 (Insulin Resistance) : Also, inactivation of the gene coding for FoxO3 enhances insulin dependent Akt phosphorylation
Højlund et al., Diabetes 2008 (Obesity...) : Impaired insulin stimulated phosphorylation of Akt and AS160 in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment ... Impaired insulin mediated total ( R ( d ) ) oxidative and nonoxidative glucose disposal ( NOGD ) was paralleled by reduced insulin stimulated Akt phosphorylation at Ser473 and Thr308 and AS160 phosphorylation in muscle of PCOS patients ... Importantly, the pioglitazone mediated improvement in insulin stimulated glucose metabolism, which did not fully reach normal levels, was accompanied by normalization of insulin mediated Akt phosphorylation at Ser473 and Thr308 and AS160 phosphorylation
Ugi et al., Mol Cell Biol 2004 : To assess this, we overexpressed small t antigen in 3T3-L1 adipocytes by adenovirus mediated gene transfer and found that the phosphorylation of Akt and its downstream target, glycogen synthase kinase 3beta, were enhanced both in the absence and in the presence of insulin
Carvalho et al., Biol Chem 2000 : We have examined the insulin stimulated IRS-2 association with PI 3-kinase and the phosphorylation of AKT/PKB , which is functionally located downstream of the PI 3-kinase, in aged ( obese ) rats
Macauley et al., J Biol Chem 2008 (Insulin Resistance) : Consistent with these observations, NButGT also does not recapitulate the impaired insulin mediated phosphorylation of Akt that is induced by treatment with PUGNAc
Benomar et al., Diabetes 2013 (Insulin Resistance) : Central resistin treatment inhibited insulin dependent phosphorylation of insulin receptor (IR), AKT , and extracellular signal related kinase 1/2 associated with reduced IR expression and with upregulation of suppressor of cytokine signaling-3 and phosphotyrosine phosphatase 1B, two negative regulators of insulin signaling
Cheng et al., Cell Metab 2009 (Diabetes Mellitus, Type 2) : Insulin stimulated activation of Akt and suppression of gluconeogenesis in hepatocytes are enhanced by APPL1 overexpression, but are attenuated by APPL1 knockdown
Zhang et al., Oncogene 2010 (Lung Neoplasms...) : Cells with reduced IR showed reduced insulin stimulated Akt activation, without affecting IGF1R activation
Buettner et al., Am J Physiol Endocrinol Metab 2007 (Insulin Resistance...) : In liver, insulin activated Akt similarly in both groups ... In muscle, insulin did not clearly activate Akt in HF-Con-AS animals, whereas insulin induced Akt phosphorylation was sustained in SHIP2-AS treated rats
Staubs et al., J Biol Chem 1998 : Furthermore, insulin activation of Akt and p70 ( s6kinase ), kinases downstream of PI3K, was unaffected by PDGF pretreatment
Hammarstedt et al., Diabetologia 2005 (Insulin Resistance) : Insulin stimulated tyrosine phosphorylation and p-ser-PKB/Akt increased, while no significant effect of thiazolidinedione treatment was seen on the inflammatory status of the adipose tissue in these non-obese subjects
Guinea Viniegra et al., Oncogene 2002 : No effect was observed in SAPK pathways ( p38MAPK and JNK ), but E1a was able to affect the Akt activation mediated by insulin
Yuzefovych et al., Endocrinology 2013 : Palmitate induced mtDNA damage, mtROS, mitochondrial dysfunction, and activation of JNK were all diminished, whereas ATP levels, mitochondrial mass, insulin stimulated phosphorylation of Akt ( Ser 473 ), and insulin sensitivity were increased in primary myotubes isolated from Tg/MTS-hOGG1 mice compared to myotubes isolated from either knockout or wild-type mice
Xiao et al., J Biol Chem 2010 (Hypoglycemia...) : The absence of SIRT6, consequently, enhances insulin signaling and activation of AKT , leading to hypoglycemia
Carlsen et al., Cell Signal 1999 (MAP Kinase Signaling System) : Insulin stimulated triacylglycerol synthesis and insulin stimulated protein kinase B/Akt activity were inhibited by the phosphatidylinositol 3-kinase inhibitors wortmannin and LY 294002, and the mitogen activated protein kinase kinase inhibitor PD 98059
Sen et al., Stem Cells 2011 : Preventing FA assembly or development of tension blocks activation of Akt by mechanical signals, but not by insulin
Yuan et al., J Biol Chem 2012 (Insulin Resistance) : Lrictor ( KO ) mice had defects in insulin stimulated Akt Ser-473 and Thr-308 phosphorylation, leading to decreased phosphorylation of Akt substrates FoxO, GSK-3ß, PRAS40, AS160, and Tsc2
Bandyopadhyay et al., Diabetes 2005 (Diabetes Mellitus, Type 2...) : Increased basal phosphorylation of Ser307 IRS-1 in the obese and type 2 diabetic subjects corresponds with decrease in insulin stimulated IRS-1 tyrosine phosphorylation, PI 3-kinase activity, and insulin induced activation of Akt and, more prominently, PKC-zeta/lambda
Ching et al., Am J Physiol Cell Physiol 2010 (Starvation) : Serum starvation did not affect p38, PKC?, or AS160 phosphorylation or insulin stimulated Akt or AS160 phosphorylation
Asilmaz et al., J Clin Invest 2004 (Disease Models, Animal...) : Leptin treatment at this dose improved insulin stimulated insulin receptor and insulin receptor substrate 2 (IRS-2) phosphorylation, IRS-2 associated PI3K activity, and Akt activity in liver
Fox et al., Am J Physiol Endocrinol Metab 2011 (Diabetic Retinopathy) : Here, we investigate the role of cholesterol enriched membrane microdomains to regulate PKC mediated inhibition of Akt dependent insulin signaling in R28 retinal neurons ... We demonstrate that PKC activation with either a phorbol ester or exogenous application of diacylglycerides impairs insulin induced Akt activation, whereas PKC inhibition augments insulin induced Akt activation ... To investigate the mechanism by which PKC impairs insulin stimulated Akt activity, we assessed various upstream mediators of Akt signaling ... Thus, we next investigated a biophysical mechanism by which insulin signaling could be disrupted and found that disruption of lipid microdomains via cholesterol depletion blocks insulin induced Akt activation and reduces insulin receptor tyrosine phosphorylation ... We also demonstrated that insulin localizes phosphorylated Akt to lipid microdomains and that PMA reduces phosphorylated Akt ... Taken together, these results demonstrate that both insulin stimulated Akt signaling and PKC induced inhibition of Akt signaling depend on cholesterol enriched membrane microdomains, thus suggesting a putative biophysical mechanism underlying insulin resistance in diabetic retinopathy
Oleksiewicz et al., J Appl Toxicol 2011 : By western blotting with phospho-specific antibodies, insulin induced phosphorylation of IRS-1, Akt , p70S6K, S6 ribosomal protein, 4E-BP1, FoxO3a, FoxO1, p44/42 MAPK and the EGFR
Wang et al., Diabetologia 2011 : After INS-1E cells were transfected with siRNA for 72 h, high glucose induced cell proliferation and insulin stimulated Akt phosphorylation were investigated ... Knockdown of Gmrp1 decreased high glucose induced cell proliferation and insulin stimulated Akt phosphorylation
Yu et al., Sheng Li Xue Bao 2013 : Also, insulin increased the phosphorylation of Akt and ERK in myoblast cells
Li et al., J Biol Chem 2013 (Diabetes Mellitus, Type 2...) : Chemical chaperones PBA and TUDCA could reverse Hcy induced inflammation and restore insulin stimulated glucose uptake and Akt activation
Ishihara et al., Biochem Biophys Res Commun 1999 : Interestingly, although both PtdIns- ( 3,4,5 ) P3 and PtdIns ( 3,4 ) P2 have been implicated in the regulation of Akt activity in vitro, overexpression of SHIP2 inhibited insulin induced Akt activation , presumably by its 5'-inositol phosphatase activity
Wang et al., Diabetes 2013 : Deletion of Paqr3 enhances insulin stimulated phosphorylation of AKT and glycogen synthase kinase 3ß, but not phosphorylation of IR and IR substrate-1 (IRS-1), in hepatocytes, mouse liver, and skeletal muscle
Ringel et al., Cancer Res 2001 (Adenocarcinoma, Follicular...) : In thyroid cancer cells, Akt 1, 2, and 3 proteins were expressed, total Akt was activated by insulin phosphatidylinositol 3'-kinase, and inhibition of phosphatidylinositol 3'-kinase reduced cell viability
Shi et al., J Biol Chem 2008 : Paradoxically, insulin stimulated Akt phosphorylation is significantly enhanced in these cells
Jessen et al., Am J Physiol Endocrinol Metab 2005 (Insulin Resistance) : GH infusion did not change Akt protein expression, and insulin caused an approximately 13-fold increase in Akt activity ( 1,309 +/- 327 and 1,287 +/- 173 % ) after both GH and saline infusion
Wick et al., J Biol Chem 2003 : In agreement with inhibited signaling through the IRS/PI 3-kinase pathway, we found hGrb10gamma to both delay and reduce phosphorylation of Akt at Thr ( 308 ) and Ser ( 473 ) in response to insulin stimulation
Ahn et al., J Biol Chem 2013 (Disease Models, Animal...) : In this study, we found that insulin directly binds to insulin receptors in Leydig cell membranes and activates phospho-insulin receptor-ß ( phospho-IR-ß ), phospho-IRS1, and phospho-AKT , leading to up-regulation of DAX-1 ( dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 ) gene expression in the MA-10 mouse Leydig cell line
Halaby et al., Biochem Biophys Res Commun 2013 : We also found that the reduction of insulin mediated Akt activity in muscle tissues of insulin resistant rats was partially reversed by chloroquine treatment
Raile et al., J Clin Endocrinol Metab 2006 (Body Weight) : Decreased IGF-IR content was accompanied by a reduction of IGF-IR/IR receptor hybrids, and therefore, increased levels of IR/IR homodimers probably explain increased insulin stimulated receptor autophosphorylation and Akt phosphorylation
Wu et al., Antioxid Redox Signal 2005 (Hyperglycemia) : Phosphorylation of the insulin receptor, IRS-1, and Akt in response to insulin was also significantly enhanced in high glucose conditions, especially at submaximal insulin concentrations
Kienesberger et al., J Biol Chem 2009 (Insulin Resistance) : In ATGL ( -/- ) mice, insulin stimulated phosphatidylinositol 3-kinase and Akt activities as well as phosphorylation of critical residues of IRS1 ( Tyr ( P ) -612 ) and Akt ( Ser ( P ) -473 ) were increased in skeletal muscle in vivo
Wada et al., Endocrinology 2009 : As a result, insulin induced phosphorylation of Akt-1 and -2 , and subsequent uptake of 2-deoxyglucose were decreased
McCall et al., J Endocrinol 2010 (Insulin Resistance) : In this report, we show that phenylmethimazole ( C10 ) blocks basal IL6 and leptin production as well as basal Socs-3 expression in fully differentiated 3T3L1 cells ( 3T3L1 adipocytes ) without affecting insulin stimulated AKT signaling
Aikin et al., Diabetologia 2006 (Cadaver) : Autocrine insulin action activates Akt and increases survival of isolated human islets ... Following overnight culture, islet conditioned medium contained significantly elevated levels of insulin, indicating that insulin may be responsible for the observed increase in Akt phosphorylation
Bernstein et al., Curr Opin HIV AIDS 2008 : Akt controls insulin signaling and is an important target in cancer, but no Akt inhibitors are approved as cancer therapeutics
Rocha et al., Endocrine 2002 : To assess insulin receptor (IR), Shc, STAT-1, ERK, and Akt phosphorylation in response to insulin in lacrimal gland and salivary gland, tissues from female and male rats ( n = 5-8/group ) were submitted to immunoprecipitation and immunoblotting or Western blotting protocol, and phosphorylation level was determined by densitometry ... In addition, in females an apparent but not significant lower STAT and Akt phosphorylation in response to insulin was observed in the lacrimal gland, compared with males
Wang et al., J Biol Chem 1998 : Furthermore, cotransfected wild-type PKB/Akt increased FAS promoter activity in the absence of insulin and a loss of insulin responsiveness of the FAS promoter ... These results demonstrate that insulin stimulation of fatty acid synthase promoter is mediated by the PI 3-kinase pathway and that PKB/Akt is involved as a downstream effector
Deblon et al., Br J Pharmacol 2012 (Fatty Liver...) : At the molecular level, long-term Sirolimus administration attenuated glucose uptake and metabolism in skeletal muscle by preventing full insulin induced Akt activation and altering the expression and translocation of glucose transporters to the plasma membrane
Sell et al., Am J Physiol Endocrinol Metab 2008 (Insulin Resistance) : CM induced insulin resistance in human myotubes at the level of insulin stimulated Akt and GSK-3 phosphorylation
Funai et al., Diabetes 2009 : To evaluate the roles of AMPK and Akt on insulin- or contraction stimulated PAS-AS160, PAS-TBC1D1, and glucose transport, rat epitrochlearis was incubated with and without compound C ( inhibitor of AMPK ) or Wortmannin ( inhibitor of phosphatidylinositol [ PI] 3-kinase, which is upstream of Akt ) before and during insulin stimulation or contraction
Schiffer et al., J Biol Chem 2004 : CD2AP was not required for PI3K/AKT activation by insulin and epidermal growth factor, indicating that CD2AP is a selective mediator of anti-apoptotic TGF-beta signaling
Chen et al., Biochemistry 2006 : siRNA mediated Gbeta1 knockdown markedly and specifically potentiates insulin dependent activation of kinase Akt , likely reflecting the removal of the inhibitory effect of Gbetagamma on PI3-Kalpha activity
Wang et al., Metabolism 2008 (Diabetes Mellitus, Type 2...) : We measured basal and insulin stimulated glucose uptake, glycogen accumulation, phosphoinositide 3 (PI-3) kinase activity, and Akt phosphorylation in primary skeletal muscle culture from subjects with type 2 diabetes mellitus incubated with or without various concentrations of PMI 5011
Kumar et al., Mol Cell Biol 2008 : In muscle lacking rictor, the phosphorylation of Akt at Ser473 was reduced dramatically in response to insulin
Qadri et al., J Biol Chem 2012 (Diabetes Mellitus, Type 2...) : HCV replicating cells demonstrated increases in cellular lipids with insulin resistance at the level of the insulin receptor, increased insulin receptor substrate 1 ( Ser-312 ), and decreased Akt ( Ser-473 ) activation in response to insulin
Aikawa et al., Circulation 2000 : Insulin strongly activated both PI3K and the putative downstream effector AKT : Moreover, a proapoptotic protein, BAD :, was significantly phosphorylated and inactivated by insulin through PI3K
Motley et al., Cell Mol Biol Incl Cyto Enzymol 2001 : Protein kinase C inhibits insulin induced Akt activation in vascular smooth muscle cells ... In this study, we specifically looked at the ability of PKC to inhibit Akt activation induced by insulin in cultured rat aortic vascular smooth muscle cells ( VSMCs ) ... A PKC activator, phorbol 12-myristate 13-acetate ( PMA ), inhibited insulin dependent Akt phosphorylation
Park et al., Diabetes 2005 (Insulin Resistance) : Basal and insulin stimulated glucose uptake in heart was significantly reduced in the MHC-PPARalpha mice, and cardiac insulin resistance was mostly attributed to defects in insulin stimulated activities of insulin receptor substrate (IRS)-1 associated phosphatidylinositol (PI) 3-kinase, Akt , and tyrosine phosphorylation of signal transducer and activator of transcription 3 ( STAT3 )
Palsgaard et al., J Biol Chem 2012 (MAP Kinase Signaling System...) : Conversely, in LRP5 knockdown preadipocytes, insulin induced phosphorylation of IRS1, Akt , GSK3ß, and ERK1/2 is highly reduced ... Wnt induces phosphorylation of Akt , ERK1/2, and GSK3ß, and this is dependent on insulin/IGF-1 receptors
Ishihara et al., FEBS Lett 2003 (Diabetes Mellitus, Type 2) : Furthermore, insulin induced phosphorylation of Akt in HIRc cells was decreased more greatly by transfection of SNP1 PTEN gene than that of wild-type PTEN gene
Park et al., Biochemistry 2000 : Insulin dependent activation of Akt was blocked by 4 h treatment with manumycin ( P < 0.01 ), a kinetic too rapid to be explained by Ras inhibition
Barazzoni et al., Kidney Int 2010 (Kidney Failure, Chronic) : Ghrelin is a gastric hormone previously shown to enhance muscle mitochondrial enzyme activities and AKT mediated insulin signaling independent of food intake in healthy rats
Lin et al., Am J Physiol Endocrinol Metab 2002 : In addition, insulin increased the apparent abundance of GS kinase ( GSK ) -3 and protein phosphatase (PP)1 alpha in the supernatant fraction of muscle homogenate to control values, and it caused the same increases in GSK-3 and Akt/protein kinase B (PKB) phosphorylation and Akt/PKB activity that it did in nondenervated muscle
Liu et al., J Int Med Res 2008 : Musclin inhibits insulin activation of Akt/protein kinase B in rat skeletal muscle
Okamoto et al., Diabetes 2007 : These results indicate that, if the hepatic abundance of glucokinase is maintained, ingested glucose is normally disposed of even in the absence of acute activation of proximal insulin signaling, such as the activation of Akt , in the liver
Sabin et al., J Cell Physiol 2007 : Using in vitro differentiated myotubes from normal weight pre-pubertal children ( n = 8 ), we examined the effects of saturated ( palmitate ) and unsaturated ( oleate ) FFAs on insulin stimulated AKT phosphorylation ( pAKT ) and IMCL accumulation
Barber et al., J Biol Chem 2001 : Insulin induced serine phosphorylation of Akt , through the phosphatidylinositol (PI) 3-kinase pathway
Rizzo et al., Mol Pharmacol 2006 : In addition, INT-747 enhances both insulin induced serine phosphorylation of Akt and glucose uptake by 3T3-L1 cells
Huang et al., Horm Res 2008 (Birth Weight...) : There was no difference of IRS-1 phosphorylation in response to insulin between two groups, however, insulin stimulated Akt phosphorylation was attenuated in NCU-SGA rats compared to appropriate for gestational age rats
Ogihara et al., Diabetes 2001 (Insulin Resistance) : Insulin induced phosphorylation of Ser-473 of Akt and Ser-21 of glycogen synthase kinase-3 also increased 2.9- and 2-fold, respectively, in the liver of the high salt fed rats
Jiang et al., Diabetes 2002 (Obesity) : In this study, we showed that, in Zucker obese ( fa/fa ) rats, acute ( 1-day ) treatment with both rosiglitazone ( a TZD ) and a non-TZD PPARgamma agonist ( nTZD ) reduced plasma free fatty acid and insulin levels and, concomitantly, potentiated insulin stimulated Akt phosphorylation at threonine 308 ( Akt-pT308 ) in adipose and muscle tissues
Heras-Sandoval et al., Neurochem Res 2012 (Insulin Resistance) : We found that insulin increased mitochondrial activity and IR/Akt phosphorylation in synaptosomes taken from both hippocampus and cortex
Rodgers et al., Mol Cell 2011 : Here we show that a downstream target of insulin induced Akt activation, Clk2, triggers Akt dephosphorylation through the PP2A phosphatase complex
Frøsig et al., Am J Physiol Endocrinol Metab 2009 : Four hours after exercise, insulin stimulated glucose uptake was improved ( approximately 70 %, P < 0.001 ) independent of diet composition and despite normal insulin stimulated regulation of insulin receptor substrate-1 associated phosphatidylinositol 3-kinase, Akt , GSK-3, and glycogen synthase
Li et al., Diabetes 2013 (Diabetes Mellitus, Type 2...) : In palmitate induced insulin-resistant C2C12 myotubes, telmisartan enhanced insulin stimulated Akt and Akt substrate of 160 kDa (AS160) phosphorylation as well as Glut4 translocation to the plasma membrane
Henkel et al., Hepatology 2009 (Insulin Resistance) : In hepatocytes, insulin stimulated glycogen synthesis and insulin dependent phosphorylation of Akt-kinase were attenuated synergistically by prior incubation with IL-6 and/or PGE ( 2 ) while insulin receptor autophosphorylation was barely affected ... In HepG2 cells expressing a recombinant EP3-receptor, PGE ( 2 ) pre-incubation activated ERK1/2, caused a serine phosphorylation of insulin receptor substrate 1 (IRS1), and reduced the insulin dependent Akt-phosphorylation ... Conclusion : PGE ( 2 ) might contribute to hepatic insulin resistance via an EP3-receptor dependent ERK1/2 activation resulting in a serine phosphorylation of insulin receptor substrate, thereby preventing an insulin dependent activation of Akt and glycogen synthesis
Barthel et al., Biochem Biophys Res Commun 1998 (Insulin Resistance) : The insulin stimulated increase in enzymatic activity of this mutant Akt was regulated by PKC activation like the wild type enzyme
Summers et al., J Biol Chem 1999 : This was particularly apparent in 3T3-L1 adipocytes overexpressing an epitope tagged form of Akt2 in which insulin activated Akt2 10-fold better than PDGF
Kwon et al., J Cell Biol 2003 : Expression of the PH-EF construct blocked endogenous PLCgamma1 binding to the IR and inhibited insulin dependent phosphorylation of mitogen activated protein kinase ( MAPK ), but not AKT
Tong et al., J Biol Chem 2010 (Carcinoma, Hepatocellular...) : Mimicking feeding effects, insulin significantly increases E4BP4 expression and binding to the Fgf21 promoter through AKT activation
Fang et al., Diabetologia 2009 : Adiponectin can also enhance insulin sensitivity via direct signalling crosstalk ; here we show that enhanced insulin stimulated IRS-1 ( Y612 ) and Akt ( T308 ) phosphorylation in response to fAd was attenuated by leptin
Gosmanov et al., Am J Physiol Endocrinol Metab 2004 (Diabetes Complications...) : Impaired expression and insulin stimulated phosphorylation of Akt-2 in muscle of obese patients with atypical diabetes ... Hyperglycemic crisis did not affect insulin stimulated threonine phosphorylation of either Akt-1 or Akt-2
Mody et al., Diabetologia 2011 (Alzheimer Disease...) : The mechanism ( s ) behind this glucose intolerance in PSEN1 and APP/PSEN1 mice appeared to involve increased levels of brain retinol binding protein 4 and basal phosphorylation of S6 ribosomal protein, and decreased insulin stimulated phosphorylation of Akt/protein kinase B and extracellular signal regulated kinase 1/2 in the brain
Boon et al., Diabetes 2013 (Diabetes Mellitus, Type 2...) : Treating cultured myotubes with LDL containing ceramide promoted ceramide accrual in cells and was accompanied by reduced insulin stimulated glucose uptake, Akt phosphorylation, and GLUT4 translocation compared with LDL deficient in ceramide
Harbrecht et al., Am J Physiol Gastrointest Liver Physiol 2012 (MAP Kinase Signaling System) : We found that SB203580 blocked insulin induced Akt activation ... NF-?B induces iNOS expression and can be regulated by Akt , but insulin had no effect on cytokine mediated I?Ba levels or NF-?B p65 translocation
Cui et al., Mol Endocrinol 2002 : Angiotensin II subtype 2 receptor activation inhibits insulin induced phosphoinositide 3-kinase and Akt and induces apoptosis in PC12W cells ... Moreover, we demonstrated that AT2 receptor stimulation inhibited insulin induced Akt phosphorylation and that insulin mediated antiapoptotic effect was also blocked by AT2 receptor activation ... Overexpression of a catalytically inactive dominant negative SHP-1 markedly attenuated the AT2 receptor- mediated inhibition of IRS-2 associated PI3K activity, Akt phosphorylation, and antiapoptotic effect induced by insulin
Summers et al., Ann N Y Acad Sci 1999 (Diabetes Mellitus, Type 2) : Interestingly, soluble analogues of ceramide antagonize both insulin 's activation of Akt/PKB as well as its stimulation of glucose transport, consistent with a causal relationship between the two
Golding et al., Mol Cancer Ther 2009 (Ataxia Telangiectasia...) : In line with this finding, the effect of KU-60019 on AKT phosphorylation was countered by low levels of okadaic acid, a phosphatase inhibitor, and A-T cells were impaired in S473 AKT phosphorylation in response to radiation and insulin and unresponsive to KU-60019
Serrano-Marco et al., Diabetes 2011 : First, we observed that the PPAR-ß/-d agonist GW501516 prevented both IL-6 dependent reduction in insulin stimulated Akt phosphorylation and glucose uptake in adipocytes
Fediuc et al., Endocrinology 2006 : We also report the novel evidence that AICAR markedly reduced insulin induced Akt-Thr308 phosphorylation after 15 and 30 min exposure to insulin, which coincided with a marked reduction in glycogen synthase kinase 3 (GSK)-3alpha/beta phosphorylation
Hittel et al., Med Sci Sports Exerc 2010 (Insulin Resistance) : A modest increase ( 44 % ) in plasma myostatin levels was also associated with significant reductions in the insulin stimulated phosphorylation of Akt ( Thr308 ) in both muscle and liver of myostatin treated animals
Nitta et al., Hepatology 2008 (Liver Cirrhosis) : In response to PI3K/Akt inhibition, CLDH had decreased basal and insulin stimulated p-Akt expression and decreased apoptosis compared to NLDH
Yano et al., Endocr J 2008 (Insulin Resistance) : insulin stimulated phosphorylation of IRS-1 and IRS-2 was impaired, the IRS-2 protein level was decreased, and insulin stimulated phosphorylation of Akt was decreased in the liver of the adipo ( -/- ) mice
Liu et al., PloS one 2012 (Insulin Resistance) : Tau phosphorylation and µ-calpain activation mediate the dexamethasone induced inhibition on the insulin stimulated Akt phosphorylation ... If so, we examined whether the DEX induced tau phosphorylation and µ-calpain activation mediate the DEX induced inhibition on the insulin stimulated Akt phosphorylation ... Finally, both LiCl pre-treatment and calpain inhibition prevented the DEX induced inhibition on the insulin stimulated Akt phosphorylation ... In conclusion, our study suggests that the tau phosphorylation and µ-calpain activation mediate the DEX induced inhibition on the insulin stimulated Akt phosphorylation
Morino et al., J Clin Invest 2005 (Body Weight...) : These changes were associated with a 50 % increase in IRS-1 Ser312 and IRS-1 Ser636 phosphorylation and an approximately 60 % reduction in insulin stimulated Akt activation in the IR offspring
Choi et al., Mol Cell Biol 2010 (Insulin Resistance) : Furthermore, insulin regulates total PKA activity in an Akt dependent manner
Jiang et al., Endocrinology 2009 : Here we showed that Akt2 , in response to insulin , resulted in phosphorylation of Clk/Sty, which then altered SR protein phosphorylation in concert with Akt2
Opel et al., Cancer Res 2007 (Neuroblastoma) : Parallel experiments in neuroblastoma cell lines revealed that activation of Akt by insulin-like growth factor (IGF)-I significantly inhibited tumor necrosis factor related apoptosis inducing ligand- or chemotherapy induced apoptosis in a PI3K dependent manner because the PI3K inhibitor LY294002 completely reversed the IGF-I mediated protection of neuroblastoma cells from apoptosis
Wu et al., Am J Physiol Endocrinol Metab 2006 (Glucose Intolerance...) : At the molecular level, a decrease in insulin stimulated Akt phosphorylation was consistent with hepatic insulin resistance
Wei et al., Am J Physiol Endocrinol Metab 2008 (Insulin Resistance) : Moreover, ANG II treatment of L6 myotubes induced NF-kappaB activation and TNF-alpha production and decreased insulin stimulated Akt activation and GLUT-4 glucose transporter translocation to plasma membranes ... Similarly, NF-kappaB p65 small interfering RNA reduced NF-kappaB p65 subunit expression and nuclear translocation and TNF-alpha production but improved insulin stimulated phosphorylation ( Ser ( 473 ) ) of Akt and translocation of GLUT-4
Halaby et al., Cell Signal 2008 (Insulin Resistance) : In addition, insulin mediated Akt phosphorylation in mouse L6 muscle cells was greatly reduced by KU-55933, a specific inhibitor of ATM
Sears et al., PloS one 2009 (Inflammation...) : Insulin stimulated Akt phosphorylation in muscle tissue from HFD fed mice was significantly greater in 12/15LO KO mice than in WT mice
Liu et al., Biochim Biophys Acta 2012 (Insulin Resistance) : C2C12 myotubes were exposed to palmitate, resulting in an increased insulin dependent Akt Ser473 phosphorylation, associated with a significant increase in the level of phosphorylation of S6K1 on T389
Finocchietto et al., PloS one 2008 (Metabolic Syndrome X) : At a precise concentration, insulin increased phospho-Akt2 that translocates to mitochondria and determines in situ phosphorylation and substantial cooperative mtNOS activation ( +4-8 fold, P < .05 ), high NO, and a lowering of mitochondrial oxygen uptake and resting metabolic rate ( -25 to -60 %, P < .05 )
Balbis et al., J Biol Chem 2004 : However, at this concentration, methyl-beta-cyclodextrin perturbed CMD of hepatocyte PM and inhibited insulin induced Akt activation and glycogen synthesis but did not affect insulin induced insulin receptor kinase tyrosine phosphorylation
Ishihara et al., Mol Endocrinol 2002 : We investigated the molecular mechanism by which SHIP2 negatively regulates insulin induced phosphorylation of Akt , a key downstream molecule of phosphatidylinositol 3-kinase important for the biological action of insulin ... Overexpression of wild-type SHIP2 ( WT-SHIP2 ) inhibited insulin induced phosphorylation of Akt at both Thr ( 308 ) and Ser ( 473 ) in Rat1 fibroblasts expressing insulin receptors ... However, on addition of a myristoylation signal, WT-SHIP2, R/Q-SHIP2, and Y/F-SHIP2 all efficiently inhibited insulin induced Akt phosphorylation at both residues, whereas a 5'-phosphatase-defective mutant SHIP2 ( deltaIP-SHIP2 ) with the myristoylation signal did not ... Furthermore, the inhibitory effect on insulin induced Akt phosphorylation by WT-SHIP2 was decreased in antisense-Shc cells ... These results indicate that the membrane localization of SHIP2 with its 5'-phosphatase activity is required for negative regulation of insulin induced Akt phosphorylation and that the localization is regulated, at least in part, by the association of SHIP2 with Shc in Rat1 fibroblasts
Barry et al., Eur J Cell Biol 2007 : PKB/Akt activity was increased by low oxygen concentrations in kidney cells, and insulin stimulated activation of PKB/Akt was stronger, more rapid and more sustained in hypoxia ... Pharmacologic stabilization of HIF1alpha independent of hypoxia did not increase insulin stimulated PKB/Akt activation
Umpierrez et al., Endocr Pract 2007 (Diabetes Mellitus, Type 2...) : Initial in vitro stimulation of muscle tissue with insulin resulted in a substantial and selectively decreased Akt-2 expression and insulin stimulated phosphorylation on the serine residue
Satoh et al., Nutrition & diabetes 2013 : Consistent with the clamp data, the insulin stimulated phosphorylation of Akt was significantly enhanced in liver but not in skeletal muscle
Somwar et al., J Biol Chem 2001 : The sensitivity of insulin stimulated activation of PKC zeta/lambda, Akt1, Akt2 , and Akt3 to wortmannin ( IC ( 50 ) = 24, 30, 35, and 60 nm, respectively ) correlated closely with inhibition of GLUT4 translocation
Biswas et al., Molecular vision 2009 : Imatinib induces apoptosis by inhibiting PDGF- but not insulin induced PI 3-kinase/Akt survival signaling in RGC-5 retinal ganglion cells ... To date, the extent of activation and the functional significance of insulin induced PI 3-kinase/Akt signaling remain unclear in the context of dysregulated PDGF receptor signaling in retinal cells ... In the present study, we tested the hypothesis that the pro-survival effect of insulin induced PI 3-kinase/Akt signaling is compromised by imatinib inhibition of PDGF receptor signaling in RGCs ... However, imatinib exposure did not affect insulin induced insulin receptor substrate (IRS) associated PI 3-kinase activity and the downstream phosphorylation of Akt , GSK-3beta, and p70S6kinase ... Together, these data indicate that disruption of PDGF receptor signaling compromises the pro-survival effect of insulin induced IRS dependent PI 3-kinase/Akt signaling in RGCs, and that the maintenance of PDGF induced PI 3-kinase/Akt signaling is critical for the survival of retinal neuronal cells
Loh et al., Cell Metab 2009 (Insulin Resistance...) : The increased insulin sensitivity in Gpx1 ( -/- ) mice was attributed to insulin induced phosphatidylinositol-3-kinase/Akt signaling and glucose uptake in muscle and could be reversed by the antioxidant N-acetylcysteine
Sanderson et al., J Neurochem 2008 (Brain Ischemia...) : We hypothesized that insulin acts through PI3-K, Akt , and Bcl-2 family proteins to inhibit cytochrome c release following transient global brain ischemia ... Moreover, insulin 's ability to inhibit cytochrome c release was completely dependent on PI3-K signaling and insulin induces phosphorylation of Akt through PI3-K ... In summary, insulin regulates cytochrome c release through PI3-K likely by activating Akt , promoting the binding between Bax and Bcl-X ( L ), and by preventing Bax translocation to the mitochondria
Isenovic et al., Exp Clin Endocrinol Diabetes 2009 (MAP Kinase Signaling System) : Insulin regulation of proliferation involves activation of AKT and ERK 1/2 signaling pathways in vascular smooth muscle cells ... Pretreatment for 15 min with 10 muM of PI3K/Akt inhibitor LY294002 or with 20 muM PD98059, inhibitor of ERK 1/2, significantly reduced INS stimulated Akt and ERK 1/2 phosphorylation by 76 and 75 %, respectively ... These results indicate that INS acts through Akt and ERK 1/2 signaling pathways to up-regulate proliferation of VSMC 's
Hagiwara et al., Cell Metab 2012 (Glucose Intolerance...) : Thus, mTORC2 regulates hepatic glucose and lipid metabolism via insulin induced Akt signaling to control whole-body metabolic homeostasis
Galbo et al., PloS one 2011 (Insulin Resistance) : Furthermore, inhibition of PP2A by specific inhibitors increased insulin stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3a
Luo et al., J Pharmacol Exp Ther 2007 : The phosphorylation of Akt , central to the PI3K pathway, was increased by both insulin ( sustained ) and EGF ( transient )
Kidd et al., J Pharmacol Exp Ther 2008 (Disease Models, Animal...) : It is noteworthy that insulin treatment induced phosphorylation of Akt in muscle and adipose tissues but did not exacerbate lipopolysaccharide (LPS) induced hypoglycemia ... The PI3K inhibitor wortmannin abolished the insulin mediated activation of Akt and the reduction of chemokine and interleukin-6 levels
Tremblay et al., Endocrinology 2005 : However, insulin induced activation of Akt was increased by rapamycin ... As in murine cells, rapamycin treatment of human adipocytes inhibited S6K1, blunted Ser636/639 phosphorylation of IRS-1, leading to increased Akt activation and glucose uptake by insulin
Kim et al., J Cell Physiol 2011 (Ion Channel Gating) : Insulin stimulation of BK ( Ca ) channels was detectable in 15 min and required activation of both Erk and Akt signaling cascades
Aoyagi et al., PloS one 2012 : The Akt inhibitor also enhanced the glucose induced insulin secretion in parallel with the upregulation of newcomer granule fusions, probably via increased motility of intracellular insulin granules
Igarashi et al., Hypertension 2001 (Diabetes Mellitus...) : In cultured vascular smooth muscle cells from fatty rats, insulin stimulated Akt ( New England Biolabs ) phosphorylation and 2-deoxy-D-glucose uptake were inhibited to 59 % and 68 %, respectively, by angiotensin II, but the effects were ameliorated by the addition of 10 ( -7 ) mol/L candesartan
Samokhvalov et al., Am J Physiol Endocrinol Metab 2009 (Insulin Resistance) : Conditioned medium from palmitate treated RAW 264.7 macrophages inhibited myoblast insulin stimulated glucose uptake, GLUT4 translocation, and Akt phosphorylation while activating JNK p38 MAPK, decreasing IkappaBalpha, and elevating inflammation markers ... Surprisingly, and opposite to its effects on adipose cells, conditioned medium from LPS treated macrophages stimulated myoblast insulin stimulated glucose uptake, GLUT4 translocation, and Akt phosphorylation without affecting stress kinases or inflammation indexes
Murata et al., PloS one 2013 : Insulin stimulated Akt phosphorylation was significantly decreased in the white adipose tissue in wild-type mice fed KD compared with those fed normal chow, but not in the muscle and liver
Pan et al., Cell cycle (Georgetown, Tex.) 2012 (Precursor Cell Lymphoblastic Leukemia-Lymphoma) : Human insulin and analogs activated AKT/mTOR signaling and stimulated ALL cell proliferation ( as measured by flow cytometric methods ), but metformin and rosiglitazone blocked AKT/mTOR signaling and inhibited proliferation
Chen et al., Mol Cell Biol 2004 (Hyperinsulinism...) : In muscle, loss of p50alpha/p55alpha results in reduced levels of insulin stimulated insulin receptor substrate 1 (IRS-1) and phosphotyrosine associated PI 3-kinase but enhanced levels of IRS-2 associated PI 3-kinase and Akt activation, whereas in adipocytes levels of both insulin stimulated PI 3-kinase and Akt are unchanged
Kokubun et al., Cell Biochem Funct 2009 : Our results suggest that in conditions of increased plasma NEFA levels, changes in insulin stimulated phosphorylation of Akt and GSK-3 and glycogen content vary differently in liver, skeletal muscles, and heart
Li et al., Endocrinology 2007 : TNF-alpha increased p38 MAPK phosphorylation, potently stimulated IRS-1 serine phosphorylation, and blunted insulin stimulated IRS-1 tyrosine and Akt phosphorylation and eNOS activity
Summers et al., J Biol Chem 1999 : S9A-GSK expression also markedly inhibited insulin stimulation of IRS-1 associated phosphatidylinositol 3-kinase activity, but only weakly inhibited insulin stimulated Akt/PKB phosphorylation and glucose uptake, with no effect on GLUT4 translocation
Chavarría et al., Dev Neurobiol 2007 : Differential, age dependent MEK-ERK and PI3K-Akt activation by insulin acting as a survival factor during embryonic retinal development ... Insulin activated both the PI3K-Akt and the MEK-ERK pathways
Perreault et al., Nat Med 2001 (Insulin Resistance...) : iNOS induction in obese wild-type mice was associated with impairments in phosphatidylinositol 3-kinase and Akt activation by insulin in muscle
Seo et al., Mol Biol Cell 2005 : When SK-N-SH cells were pretreated with the NADPH oxidase inhibitor diphenyleneiodonium chloride before insulin stimulation, insulin mediated translocation of PDK-1 to the membrane fraction and phosphorylation of Akt were remarkably reduced, whereas PI-3 kinase activity was not changed significantly
Sakaue et al., Mol Endocrinol 1997 : A serine/threonine kinase Akt , a constitutively active mutant of which was previously shown to stimulate glucose uptake, is activated by insulin , GH, and hyperosmolarity to approximately 4-fold, approximately 2.1-fold, and approximately 2.3-fold over basal level, respectively
Johnson et al., Proc Natl Acad Sci U S A 2006 : Physiological levels of insulin did not increase Akt phosphorylation, and the protective effects of insulin were only partially altered in islets lacking 80 % of normal Akt activity, suggesting the presence of additional insulin regulated antiapoptotic pathways
Li et al., BMC neuroscience 2011 : Expression of Asb-4 decreased both basal and insulin stimulated phosphorylation of AKT at Thr308
Mayer et al., Regul Pept 2010 : Insulin significantly increased Akt phosphorylation, but no changes were observed after angiotensin II injection in vehicle pretreated animals
Arribas et al., J Biol Chem 2003 : Downstream of PI 3-kinase, IRS-3 expression restored insulin induced Akt phosphorylation, which is impaired by the lack of IRS-1 signaling ... In brown adipocytes expressing the IRS-3F4 mutant, the association of the p85alpha regulatory subunit via Src homology 2 binding was lost, but insulin nevertheless induced PI 3-kinase activity and Akt phosphorylation in a wortmannin dependent manner
Hill et al., Mol Cell Biol 1999 : Moreover, insulin , but not PDGF, stimulated the translocation of PKBbeta to the plasma membrane and high-density microsome fractions of 3T3-L1 adipocytes
Goustin et al., Cell Signal 2013 : Here we show that Ahsg blocks insulin stimulated GLUT4 translocation and Akt activation in intact cells ( mouse myoblasts )
Bouzakri et al., Diabetes 2006 (Insulin Resistance) : Insulin action on ERK-1/2 and Akt phosphorylation was impaired in pancreas-kidney transplant recipients and was preserved in nondiabetic kidney transplant recipients
Kim et al., Proteomics 2009 : Since the silencing of gC1qR by small RNA interference abolished adipogenesis and blocked insulin induced activation of insulin receptor, insulin receptor substrate-1 (IRS-1), Akt , and Erk1/2, we can conclude that gC1qR is an essential molecule involved in adipogenesis and insulin signaling
Madonna et al., Thromb Haemost 2009 (Hyperinsulinism) : In short-term incubations, insulin did not affect constitutive Akt and eNOS at any concentration, but significantly increased their active phosphorylated forms, and NO production
Lin et al., Mol Nutr Food Res 2008 (Carcinoma, Hepatocellular...) : We found that the high glucose condition causes significant increasing Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1), leading to reduce insulin stimulated phosphorylation of Akt
Nihei et al., Clin Exp Pharmacol Physiol 2005 : It was found that Akt was activated in the presence of insulin
Yang et al., J Biol Chem 2013 (Diabetes Mellitus...) : The leucine facilitated insulin induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was blocked by inhibition of c-Src ( PP2 ), PI3K ( LY294002 ), Gai protein ( pertussis toxin or siRNA against Gai1 gene, or ß-arrestin 2 ( siRNA ) )
Sasaoka et al., Pharmacol Ther 2006 (Atherosclerosis...) : Overexpression of PTEN and SKIP also inhibited insulin induced phosphorylation of Akt and the uptake of glucose in cultured cells
Teruel et al., Diabetes 2001 (Insulin Resistance) : C2-ceramide completely abolished insulin stimulated Akt/protein kinase B phosphorylation on regulatory residues Thr 308 and Ser 473, as did TNF-alpha, and inhibited insulin induced mobility shift in Akt1 and Akt2 separated in PAGE
Zhang et al., J Hypertens 2008 (Disease Models, Animal...) : Moreover, peroxisome proliferator activated receptor ( PPAR)gamma and phosphatidylinositol 3 (PI-3) kinase p85 expression and insulin induced Akt phosphorylation were reduced in SHR cardiomyocytes, but were markedly restored when animals were treated with rosiglitazone for 14 days
Burghoff et al., Arch Physiol Biochem 2013 (Dyslipidemias...) : Additionally, insulin induced Akt phosphorylation is reduced in skeletal muscle of CD73 ( -/- ) mice
Shigematsu et al., J Biol Chem 2001 : Consistent with this observation, insulin stimulated the phosphorylation of Akt in the caveolin 2- and GLUT4 positive cells, whereas PDGF primarily stimulated Akt phosphorylation in the caveolin 2- and GLUT4 negative cell population
Shimizu et al., Endocrinology 2002 : Even though the decrease in insulin receptor substrate protein-1 ( IRS-1 ) phosphorylation was identical with that seen in L6 myocytes, overexpression of wild-type PTP1B in L1 adipocytes was associated with modest impairment of insulin stimulated Akt phosphorylation in addition to a small, but significant, attenuation in insulin stimulated glucose uptake, when compared with a phosphatase negative mutant
Krämer et al., Diabetes 2005 : Basal and insulin stimulated protein kinase B/Akt was unaltered in cells preexposed to PPARdelta agonists
Macia et al., Diabetes 2012 (Inflammation...) : Importantly, treatment of adipocytes with the supernatant of activated Y1-deficient macrophages causes insulin resistance, as demonstrated by decreased insulin induced phosphorylation of the insulin receptor and Akt as well as decreased expression of insulin receptor substrate 1
Zhang et al., PloS one 2011 (Thinness) : Insulin caused the same dose dependent increase of Akt phosphorylation in hepatocytes from ad libitum ZL and ZF rats
Ijuin et al., J Biol Chem 2012 : Suppression of SKIP significantly increased the insulin stimulated phosphatidylinositol 3,4,5-trisphosphate levels and Akt phosphorylation
Doronzo et al., Diabetologia 2006 (Insulin Resistance) : It is also reduced in Zucker fa/fa rats, which present an impaired ability of insulin to induce Akt , ERK-1/2 and JNK-1/2 phosphorylation
Ohashi et al., Cancer Sci 2012 (Biliary Tract Neoplasms) : BMS-536924 blocked autophosphorylation of IGF-IR and both Akt and ERK activation by both IGF-I and insulin
Hernandez et al., FEBS Lett 2001 : Akt mediates insulin induction of glucose uptake and up-regulation of GLUT4 gene expression in brown adipocytes
Oku et al., Am J Physiol Endocrinol Metab 2001 (Diabetes Mellitus, Experimental...) : Inhibitory effect of hyperglycemia on insulin induced Akt/protein kinase B activation in skeletal muscle ... Similarly, insulin induced phosphorylation and activation of Akt/protein kinase B (PKB) and GLUT-4 translocation were severely impaired ... The amelioration of hyperglycemia by T-1095, a Na ( + ) -glucose transporter inhibitor, normalized the reduced insulin sensitivity in the soleus muscle and the impaired insulin stimulated Akt/PKB phosphorylation and activity
Zhang et al., Proc Natl Acad Sci U S A 2012 : GPAT1 overexpression impaired insulin stimulated phosphorylation of Akt-S473 and -T308 , diminished insulin-suppression of glucose production, significantly inhibited mTOR complex 2 (mTORC2) activity and decreased the association of mTOR and rictor
Ueki et al., Proc Natl Acad Sci U S A 2002 : Moreover, insulin induced activation of AKT was significantly up-regulated in muscle from the p85beta ( -/- ) mice
Boström et al., Biochem Soc Trans 2009 (Insulin Resistance) : Syntaxin-5 is low in T2D patients, which leads to a decrease in the insulin dependent phosphorylation of Akt ( also known as protein kinase B )
Su et al., Am J Physiol Heart Circ Physiol 2012 : Insulin stimulation induced translocation of phosphorylated Akt to the mitochondria in primary cardiomyocytes
Fagan et al., Cancer Res 2012 (Breast Neoplasms) : An IGF1R tyrosine kinase inhibitor, AEW541, with equal potency for the IGF1R and IR, inhibited IGF-I-, IGF-II-, and insulin stimulated Akt phosphorylation, proliferation, and anchorage independent growth in parental cells
Yao et al., Am J Physiol Regul Integr Comp Physiol 2008 (Insulin Resistance...) : In EtOH compared with pair fed and control offspring, basal and pyruvate induced blood glucose was increased, insulin induced PDK1, Akt , and PKCzeta phosphorylation was reduced, and expression of PTEN and TRB3 was increased while their acetylation status was decreased in association with increased HDAC and decreased HAT activities
Højlund et al., Diabetologia 2006 : Insulin increased Akt phosphorylation at Ser473 and Thr308, inhibited glycogen synthase kinase-3alpha activity, reduced phosphorylation of glycogen synthase at sites 3a+3b, and increased glycogen synthase activity in Arg1174Gln carriers ( all p < 0.05 ) ... In vivo insulin signalling in skeletal muscle of patients harbouring the Arg1174Gln mutation is surprisingly intact, with modest impairments in insulin stimulated activity of Akt and glycogen synthase explaining the moderate degree of insulin resistance
Feng et al., Biosci Biotechnol Biochem 2012 (Insulin Resistance) : In it, palmitate decreased insulin stimulated glucose uptake and consumption in a dose dependent manner, and it reduced the insulin stimulated phosphorylation of Akt at Thr308 and Ser473, but had no effect on the protein expression of PI3K-p85 or the activity of PI3K
Taniyama et al., Arterioscler Thromb Vasc Biol 2005 : Using Western analysis, we found that angiotensin II ( 100 nmol/L ; 18 hours ) caused a 61+/-5 % degradation of IRS-1 and abolished insulin induced activation of Akt
Chen et al., Proc Natl Acad Sci U S A 2006 : In keeping with these data, Ucn 2 inhibited insulin induced Akt and ERK1/2 phosphorylation in cultured skeletal muscle cells and C2C12 myotubes
Takaguri et al., J Pharmacol Sci 2008 : Insulin induced tyrosine phosphorylation of IRS-1 and serine/threonine phosphorylation of Akt were reduced by atorvastatin
Serrano et al., Mech Ageing Dev 2009 (Insulin Resistance) : In liver, we found no major differences in the ability of insulin to induce autophosphorylation of the IR or activation of Akt between adult and old animals
Kim et al., J Biol Chem 2009 (Diabetes Mellitus, Type 2...) : Excess amino acids inhibited insulin stimulated Akt phosphorylation and glycogen synthesis in mouse primary hepatocytes as well as in human hepatocarcinoma HepG2 cells
Duda et al., Kardiol Pol 2006 (Cardiomegaly...) : Hypertensive patients with high plasma insulin or metabolic syndrome have a greater occurrence of LVH, which could be due to insulin activation of the serine-threonine kinase Akt and its downstream targets in the heart, resulting in cellular hypertrophy
Asrih et al., J Mol Cell Cardiol 2013 : In cardiomyocytes exposed to 1nM CT-1 there was also reduced phosphorylation of Akt and AS160 in response to insulin , and of AMPK in response to oligomycin ... On the other hand in cardiomyocytes exposed to 10nM CT-1 there was increased phosphorylation of the AS160 and Akt in response to insulin
Zhang et al., Mol Endocrinol 2008 (Inflammation...) : Reducing LCN2 gene expression causes decreased expression of PPARgamma and adiponectin, slightly reducing insulin stimulated Akt2 phosphorylation at Serine 473 in 3T3-L1 adipocytes
Kupriyanova et al., J Biol Chem 1999 : Akt-2 is found to be recruited to Glut4 containing vesicles in response to insulin
Ben-Romano et al., Diabetologia 2004 (Insulin Resistance) : Yet insulin induced phosphorylation of Akt/protein kinase B (PKB), p70S6 kinase and extracellular signal regulated kinase 1/2 was significantly impaired
He et al., Arterioscler Thromb Vasc Biol 2006 (Insulin Resistance...) : This was associated with a parallel 40 % inhibition of insulin stimulated activation of both Akt and VEGF expression in the myocardium and cardiomyocytes
Vuguin et al., Diabetes 2004 (Body Weight...) : Insulin stimulated insulin receptor substrate 2 and Akt-2 phosphorylation were significantly blunted in IUGR rats
Pandey et al., J Cardiovasc Pharmacol 2007 (Hypertension) : Immunoblotting revealed that hyperglycemia and PPAR-gamma inhibition significantly ( P < 0.001 ) decreased insulin stimulated insulin receptor (IR)-beta, Akt , and glycogen synthase kinase (GSK)-3beta phosphorylation, whereas phosphotyrosine phosphatase (PTP)-1B expression was increased in VSMC from both strains
Higuchi et al., Am J Physiol Heart Circ Physiol 2006 : Both basal and insulin stimulated Akt phosphorylation were reduced by almost 70 % by TNF-alpha overexpression
Qin et al., J Bioenerg Biomembr 2012 (Insulin Resistance) : These changes were accompanied by a marked upregulation in expression of insulin stimulated tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt following treatment with a-LA
Kanan et al., J Neurochem 2010 : In our previous studies, we have shown that insulin receptor (IR) activation leads to the activation of phosphoinositide 3-kinase (PI3K) and Akt activation in rod photoreceptors
Sweeney et al., Endocrinology 2001 : Preincubation of cells with leptin also had no effect on insulin stimulated tyrosine phosphorylation of insulin receptor, IRS-1 and IRS-2, phosphatidylinositol 3-kinase activity, or Akt phosphorylation
Ormazabal et al., Horm Metab Res 2013 : However, in testosterone treated cells acute insulin stimulation did not increase phospho-S473Akt and phospho-Y14caveolin-1 levels and reduced 2-DOG uptake was observed compared to control cells
Ruffolo et al., J Biol Chem 2007 (Insulin Resistance) : The increased basal activity of p70S6K in PTP-1B-/- adipose correlated with decreases in IR substrate-1 protein levels and insulin stimulated Akt/protein kinase B activity, explaining the decrease in insulin sensitivity even as insulin receptor phosphorylation was unaffected
Li et al., Diabetes 2013 (Inflammation) : Insulin stimulated Akt phosphorylation and glucose uptake are impaired in SNRK knockdown adipocytes
Marucci et al., Biochim Biophys Acta 2013 : In addition, GALNT2 down-regulation reduced insulin stimulation of IR, IRS-1 and Akt phosphorylation and insulin inhibition of phosphoenolpyruvate carboxykinase ( PEPCK ) expression, a key neoglucogenetic enzyme
Kim et al., J Nutr Biochem 2012 : One such case is the prevention of FoxO1 expression by activated insulin induced phosphatidylinositol 3-kinase (PI3K)/Akt , which leads to increased oxidative stress and aging processes
Zhong et al., Br J Pharmacol 2008 (Insulin Resistance) : In addition, Ang II diminished insulin stimulated phosphorylation of Akt ( at Ser ( 473 ) ) and eNOS ( at Ser ( 1177 ) ) and NO generation, effects which were reversed by ACE2 gene transfer and anti-MIF treatment in endothelial cells
Ussher et al., Diabetes 2010 (Body Weight...) : DIO mice treated with myriocin showed a complete reversal of glucose intolerance and insulin resistance which was associated with enhanced insulin stimulated Akt and glycogen synthase kinase 3ß phosphorylation
Tsuneki et al., Neuropeptides 2013 : In addition, insulin induced phosphorylation of Akt in the liver was impaired in orexin-deficient but not wild-type mice after chronic stress
Wang et al., Diabetes 2011 (Insulin Resistance...) : In endothelial cells, APPL1 potentiated insulin stimulated Akt activation by competing with the Akt inhibitor Tribbles 3 (TRB3) and suppressed ERK1/2 signaling by altering the phosphorylation status of its upstream kinase Raf-1
Ikonomov et al., Exp Cell Res 2007 : Loss of PIKfyve-ArPIKfyve reduced insulin stimulated Akt phosphorylation and the cell surface accumulation of GLUT4 or IRAP, but not GLUT1 containing vesicles without affecting overall expression of these proteins
Ishikura et al., Biochem Biophys Res Commun 2007 : The Rab GTPase activating protein ( Rab-GAP ) AS160 is inhibited upon phosphorylation by insulin activated Akt , thereby allowing GLUT4 translocation
Chang et al., Endocrinology 2007 : In contrast, loss of TC10alpha had no effect on the stimulation of Akt by insulin
Nemoto et al., Am J Physiol Heart Circ Physiol 2011 (Diabetes Mellitus, Type 2...) : The insulin stimulated phosphorylation levels of Src/PDK1/Akt/eNOS , but not of Pyk2, were decreased by PP2 in control and losartan treated GK, but not in GK, aortas
Kim et al., J Pharmacol Exp Ther 2006 : These results show that PI3K/Akt/p70S6K signaling is active in the insulin mediated up-regulation of the antioxidant defense system and that low insulin levels, as encountered in diabetes, potentially increase the susceptibility of hepatocytes to xenobiotic mediated and/or oxidative stress mediated damage
Samane et al., Evidence-based complementary and alternative medicine : eCAM 2006 : In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin induced PKB/Akt activation
Schubert et al., Proc Natl Acad Sci U S A 2004 (Insulin Resistance...) : Thus, lack of insulin signaling in the brain may lead to changes in Akt and GSK3 beta activity and Tau hyperphosphorylation but must interact with other mechanisms for development of Alzheimer 's disease
Barthel et al., J Biol Chem 1999 (Liver Neoplasms, Experimental) : In order to selectively turn on the Akt kinase cascade, we expressed a hydroxytamoxifen-regulatable form of Akt ( myristoylated Akt1 estrogen receptor chimera ( MER-Akt1 ) ) in the Hepa1c1c7 cells ; we verified that hydroxytamoxifen stimulates MER-Akt1 activity to a similar extent as the activation of endogenous Akt by insulin
Meier et al., Cell Physiol Biochem 2008 : Deprivation of insulin for 24 and 48 h reduced basal and insulin stimulated IR-kinase activity, IRS-1 phosphorylation, p85 association with IRS-1 and Ser ( 273 ) -phosphorylation of Akt by 30-40 % and increased C3-activity by 15-20 % ( p < 0.01, respectively )
Hadsell et al., J Endocrinol 2007 (Weight Loss) : Decreased lactation capacity and altered milk composition in insulin receptor substrate null mice is associated with decreased maternal body mass and reduced insulin dependent phosphorylation of mammary Akt ... The loss of IRS-1 was associated with a compensatory increase in insulin induced IRS-2 phosphorylation ; however, the loss of IRS-1 did also cause a reduction in insulin dependent mammary gland-specific activation of Akt phosphorylation ... These results support the conclusion that IRS-1 is important for insulin dependent activation of Akt signaling within the lactating mammary gland, but that loss of this protein has only modest impact on normal milk synthesis, since related signaling proteins such as IRS-2 may act in compensatory fashion
Ghosh et al., Endocrinology 2007 (Insulin Resistance) : Western blot analysis of L6 cell lysates demonstrated impaired insulin stimulated phosphorylation of Akt , serine/arginine-rich protein 40, and glycogen synthase kinase 3beta in response to TNFalpha and the short chain C6 ceramide analog
Nikoulina et al., J Clin Endocrinol Metab 2001 (Diabetes Mellitus, Type 2) : Protein expression of IRS-1, p85, p110, Akt, p70 S6 kinase, and MAPK were normal in diabetic cells, as was insulin stimulated phosphorylation of Akt , p70 S6 kinase, and MAPK
Okamoto et al., J Clin Invest 2005 (Hyperinsulinism...) : Analyses of protein expression indicated that L1 mice had modestly reduced Insr content but normal insulin stimulated Akt phosphorylation in the liver ... Conversely, L1 mice had a near complete ablation of Insr protein product in the arcuate and paraventricular nuclei of the hypothalamus, which was associated with a failure to undergo insulin dependent Akt phosphorylation in the hypothalamus
Weng et al., Hum Mol Genet 2002 (Breast Neoplasms) : In contrast, the PI3K inhibitor LY492002 has no effect on insulin stimulated phosphorylation of ETS-2, despite the fact that it diminishes insulin stimulated phosphorylation of Akt
Yan et al., J Endocrinol 2013 (Glucose Intolerance...) : In addition, prenatal DHT treatment significantly decreased insulin stimulated phosphorylation of AKT in the skeletal muscles of 6-week-old PNA rats
Rosenblatt-Velin et al., FASEB J 2004 (Insulin Resistance) : Insulin mediated phosphorylation of Akt was not reduced, indicating that activation of phosphatidylinositol 3-kinase (PI3K) was preserved
Alonso-Magdalena et al., Environ Health Perspect 2010 (Prenatal Exposure Delayed Effects) : Insulin stimulated Akt phosphorylation was reduced in skeletal muscle and liver of BPA treated pregnant mice relative to controls
Liu et al., Acta Pharmacol Sin 2008 (Insulin Resistance) : Resistin attenuated multiple effects of insulin, including insulin stimulated glycogen synthesis and phosphorylation of IRS, protein kinase B/Akt , as well as GSK-3beta
Tan et al., J Biol Chem 2010 : Studies of isolated Appl1 ( -/- ) murine embryonic fibroblasts ( MEFs ) showed that Akt activation by epidermal growth factor, insulin , or fetal bovine serum was similar to that observed in wild-type MEFs, although Akt activation by HGF was diminished in Appl1 ( -/- ) MEFs
Fuglesteg et al., Basic Res Cardiol 2008 (Disease Models, Animal...) : Insulin given at reperfusion led to phosphorylation of STAT3 and Akt both of which were inhibited by AG490
Song et al., PloS one 2013 (Body Weight...) : The specific mechanism mediating the effects of BP revealed that insulin stimulated phosphorylation of Akt was strongly decreased, and its downstream substrate, phospho-GSK3ß, was downregulated by BPE treatment in 3T3-L1 cells
Shen et al., J Biol Chem 2004 (Body Weight...) : Treatment with LG268 increases insulin stimulated IRS-1 tyrosine phosphorylation and Akt phosphorylation in skeletal muscle without affecting the activity of the CAP/c-Cbl pathway
Giani et al., Am J Physiol Heart Circ Physiol 2007 : Acute in vivo insulin induced cardiac Akt phosphorylation was inhibited by ANG II
Kim et al., BMC complementary and alternative medicine 2012 (Insulin Resistance...) : Interestingly, CAF diminished the insulin stimulated serine phosphorylation of Akt ( Ser473 ) and GSK3ß ( Ser9 ), which may reduce glucose uptake in response to insulin and lipid accumulation
Steppan et al., Mol Cell Biol 2005 (Insulin Resistance) : Here we show that in 3T3-L1 adipocytes, resistin attenuates multiple effects of insulin, including insulin receptor (IR) phosphorylation, IR substrate 1 (IRS-1) phosphorylation, phosphatidylinositol-3-kinase (PI3K) activation, phosphatidylinositol triphosphate production, and activation of protein kinase B/Akt
Egawa et al., Endocrinology 2000 (Insulin Resistance) : Recently, we have reported that the overexpression of a membrane targeted phosphatidylinositol (PI) 3-kinase ( p110CAAX ) stimulated p70S6 kinase, Akt , glucose transport, and Ras activation in the absence of insulin but inhibited insulin stimulated glycogen synthase activation and MAP kinase phosphorylation in 3T3-L1 adipocytes
Dominici et al., Mech Ageing Dev 2003 (Dwarfism) : However, insulin stimulated phosphorylation of Akt was slightly reduced ( by 20 % ), suggesting that the attenuation of insulin signaling downstream PI 3-kinase may involve other signaling molecules
Orzechowski et al., Life Sci 2005 : Preincubation with sodium ascorbate potentiates insulin dependent PKB/Akt and c-Jun phosphorylation in L6 rat myoblasts challenged with reactive oxygen/nitrogen species ... A short-term treatment experiment ( 0 - 45 min ) revealed that either insulin ( 0.1 muM ) or hydrogen peroxide ( 0.1, 0.5 mM ; H2O2 ) increased the pS473-Akt and pS63, pS73-c-Jun protein levels, although the effect of ROS/RNS peaked earlier ( 5 min ) than that of insulin ( 45 min ) ... Astonishingly, the elevated levels of both pS473-Akt and pS63, pS73-c-Jun in response to insulin were reduced by the concomitant treatment with H2O2 in a dose dependent fashion
Sharma et al., Cardiovasc Res 2007 : Although insulin enhanced Akt activity, phosphorylation of mTOR and its downstream targets ( p70S6K and 4EBP1 ) required the addition of glucose
Zhang et al., Proc Natl Acad Sci U S A 2007 (Fatty Liver...) : The defects in insulin action were associated with an approximately 40 % reduction in insulin stimulated insulin receptor substrate-2 associated phosphatidylinositol 3-kinase activity and an approximately 50 % decrease in Akt2 activation
Moon et al., Am J Physiol Endocrinol Metab 2003 : Insulin stimulated phosphorylation of Akt/protein kinase B-alpha, one of the downstream targets of PI 3-kinase and p38 MAPK phosphorylation, was also not affected by resistin
Huang et al., Mol Cell Neurosci 2005 : Insulin also induced rapid and long-term ( 30 h ) PI 3-K dependent phosphorylation of Akt and cAMP response element binding protein ( CREB )
Fuglesteg et al., Acta Physiol (Oxf) 2009 (Myocardial Infarction) : However, the putative Akt inhibitor, although capable of abolishing cardioprotection induced by insulin, was not able to inhibit insulin induced phosphorylation of Akt in Langendorff perfused rat hearts and cultured HL1 cells
Shen et al., Pediatr Res 2005 : Insulin increased PKB/Akt phosphorylation and p70S6K phosphorylation to a similar extent as in fed animals
Blero et al., Biochem Biophys Res Commun 2001 : Overexpression of SHIP2 led to a decrease of the insulin dependent PIP3 production as well as Akt/PKB activation and MAPK stimulation
Kwon et al., Nutrition 2011 : This improvement was associated with insulin/insulin-like growth factor-1 signaling that was activated by the tyrosine phosphorylation of insulin receptor substrate-2 and serine phosphorylation of Akt , and this in turn increased pancreatic and duodenal homeobox-1 expression
Mawatari et al., Asia Pac J Clin Nutr 2008 (Insulin Resistance) : Treatment with 100 M diamide suppressed significantly insulin induced IRS and Akt phosphorylation
Wang et al., Diabetes 2009 (Insulin Resistance) : Skeletal muscle triglyceride was 38 % lower, and insulin stimulated phosphorylated Akt ( Ser473 ) was twofold greater in SMLPL ( -/- ) mice without changes in IRS-1 tyrosine phosphorylation and phosphatidylinositol 3-kinase activity
Mondal et al., The Ochsner journal 2013 : Insulin induced PI3K/Akt signaling and endothelial nitric oxide ( NO ) -synthase ( eNOS ) phosphorylation regulates NO production by ECs that maintain vascular homeostasis ... NEL suppressed insulin induced phosphorylation of both Akt and eNOS at serine residues 473 and 1177, respectively
Xie et al., Lipids 2006 (Insulin Resistance) : These findings were associated with increased basal phosphorylation of perilipin, increased Glut-1 but decreased Glut-4 expression, and reduced insulin induced Akt phosphorylation
Won et al., Obesity (Silver Spring) 2009 (Obesity) : ICV administration of TG by itself activated signal-transduction-activated-transcript-3 ( STAT3 ) and Akt in the hypothalamus, but prevented a further activation of hypothalamic STAT3 and Akt by leptin and insulin
Montessuit et al., Endocrinology 2008 (Insulin Resistance) : Phosphorylation of Akt and AS160 in response to insulin was lower in insulin-resistant cardiomyocytes
Fleming et al., Thromb Haemost 2003 : Insulin activated the protein kinase Akt in cultured endothelial cells and increased the phosphorylation of eNOS on Ser ( 1177 ) but failed to increase endothelial cyclic GMP levels or to elicit the relaxation of endothelium-intact porcine coronary arteries
Csibi et al., PloS one 2010 : Angiotensin II inhibits insulin stimulated GLUT4 translocation and Akt activation through tyrosine nitration dependent mechanisms ... Inhibition of nitric oxide synthase and NAD ( P ) Hoxidase and scavenging of free radicals with myricetin restored insulin stimulated Akt phosphorylation and GLUT4 translocation in the presence of Ang II
Guo et al., Am J Physiol Cell Physiol 2005 : In serum starved ML-1 cells, insulin rapidly stimulated phosphorylation of ERK1/2 and Akt , and the phosphorylation levels peaked approximately 30 min after treatment
Taguchi et al., Diabetes 2012 : G protein coupled receptor kinase 2, with ß-arrestin 2, impairs insulin induced Akt/endothelial nitric oxide synthase signaling in ob/ob mouse aorta ... In type 2 diabetes, impaired insulin induced Akt/endothelial nitric oxide synthase (eNOS) signaling may decrease the vascular relaxation response ... 2 ) Insulin stimulated Akt and eNOS phosphorylations were decreased
Galic et al., Mol Cell Biol 2003 (MAP Kinase Signaling System) : In immortalized TCPTP ( -/- ) murine embryo fibroblasts, insulin induced IR beta-subunit tyrosine phosphorylation and protein kinase PKB/Akt activation were enhanced relative to the values in TCPTP ( +/+ ) cells
Yamada et al., J Cell Biol 2005 : These data demonstrate that insulin activation of Akt2 specifically regulates the docking/fusion step of GLUT4 containing vesicles at the plasma membrane through the regulation of Synip phosphorylation and Synip-Syntaxin4 interaction
Teshima et al., Life Sci 2010 (Necrosis) : However, high-glucose condition attenuated the insulin induced Akt phosphorylation and cardioprotection
Ling et al., Exp Clin Endocrinol Diabetes 2012 (Hyperglycemia...) : Moreover, over expressing miR-21 significantly increased insulin induced phosphorylation of AKT ( Ser473 ), GSK3ß ( Ser9 ) and the translocation of glucose transporter 4 (GLUT4) in IR-adipocytes.In this study, our data demonstrate that miR-21 reverses high glucose and high insulin induced IR in 3T3-L1 adipocytes, possibly through modulating the PTEN-AKT pathway, and miR-21 may be a new therapeutic target for metabolic diseases such as T2DM and obesity
Li et al., Endocrinology 2009 (Acute Disease...) : In the liver, the defects of insulin signaling after hemorrhage, including reduced tyrosine phosphorylation of the insulin receptor and IRS-1, association between IRS-1 and phosphatidylinositol 3-kinase and serine phosphorylation of Akt in response to insulin were not altered by pretreatment of rats with metyrapone or RU486
Igarashi et al., Diabetes Res Clin Pract 2007 (Diabetes Mellitus, Experimental...) : Insulin stimulated Akt phosphorylation and 2-deoxy-d-glucose uptake in WF were significantly reduced by Ang II, and the reduction was ameliorated by olmesartan but not PD123,319
Ching et al., Applied physiology, nutrition, and metabolism = Physiologie appliquée, nutrition et métabolisme 2013 : There are reports that ataxia telangiectasia mutated (ATM) plays a role in insulin stimulated Akt phosphorylation, although this is not the case in some cell types ... Because Akt plays a key role in insulin signaling, which leads to glucose transport in skeletal muscle, the predominant tissue in insulin stimulated glucose disposal, we examined whether insulin stimulated Akt phosphorylation and ( or ) glucose transport would be decreased in skeletal muscle of mice lacking functional ATM, compared with muscle from wild-type mice ... We found that in vitro insulin stimulated Akt phosphorylation was normal in soleus muscle from mice with 1 nonfunctional allele of ATM ( ATM+/- ) and from mice with 2 nonfunctional alleles ( ATM-/- ) ... However, in contrast to findings for soleus, insulin stimulated Akt phosphorylation was blunted in ATM-/- EDL, concomitant with a tendency for insulin stimulated phosphatidylinositol 3-kinase activity to be decreased
King et al., J Biol Chem 2004 : The interaction of PDK-1 with Grb14 facilitates Akt function : disruption of the interaction by overexpression of a construct of Grb14 mutated in the PDK-1 binding motif significantly decreases insulin dependent activation of Akt
Luo et al., Endocrinology 2007 : These results suggest that a feed-forward mechanism may exist whereby insulin activation of Akt leads to phosphorylation of IRS-1 at Ser ( 629 ), resulting in decreased phosphorylation of IRS-1 at Ser ( 636 ) and enhanced downstream signaling
Sparks et al., Biochem Biophys Res Commun 2013 : Vps34 inhibition of IDAD occurs without altering insulin dependent S473 phosphorylation of Akt indicating PI3K/PIP3/Akt signaling is intact
Kagawa et al., J Clin Endocrinol Metab 2005 : Transfection study showed that expression of SNP3-SHIP2 inhibited insulin induced PI ( 3,4,5 ) P3 production and Akt2 phosphorylation less potently than expression of wild-type SHIP2 in CHO-IR cells
Ropelle et al., J Physiol 2009 (Obesity) : Results demonstrate that acute exercise improved insulin signalling, increasing insulin stimulated Akt and Foxo1 phosphorylation and decreasing PGC-1alpha expression and PGC-1alpha/Foxo1 interaction in the liver of diet induced obesity rats under fasting conditions
Sartorius et al., Cell Physiol Biochem 2012 : Leptin treatment led to a significant decrease in insulin mediated phosphorylation of the insulin receptor and Akt473 which was accompanied by a decline in glycogen synthesis in primary astrocytes and significantly decreased insulin induced phosphorylation of the insulin receptor and insulin receptor substrate-2 in brain tissues of mice
Li et al., Eur J Pharmacol 2008 : In addition, salidroside enhanced insulin mediated Akt activation and glucose uptake, and such enhancement can be specifically inhibited by compound C
Sugita et al., Metabolism 2012 (Burns...) : Insulin stimulated activation ( phosphorylation ) of IR, IRS-1, and Akt was assessed by immunoblotting and immunoprecipitation ... The increase of iNOS expression paralleled the increase of insulin resistance, as evidenced by decreased tyrosine phosphorylation of IR and IRS-1, IRS-1 expression, insulin stimulated activation of phosphatidylinositol 3-kinase and Akt/PKB , and insulin stimulated glucose uptake in mouse skeletal muscle
Andersson et al., BMC cell biology 2007 (Neuroblastoma) : Baculovirus mediated gene transfer and recombinant protein expression do not interfere with insulin dependent phosphorylation of PKB/Akt in human SHSY-5Y and C3A cells
Kim et al., Diabetes 1999 (Hyperinsulinism) : Insulin for 1 min stimulated Akt/PKB activity approximately 5-fold in both saline- and glucosamine infused rats ; insulin induced hyperphosphorylation of Akt/PKB was not different between groups
Zhang et al., Endocrinology 2013 : In addition, insulin at the physiological range inhibited CSE expression, and H ( 2 ) S decreased insulin stimulated phosphorylation of Akt in HepG ( 2 ) cells
Mitsuuchi et al., J Cell Biochem 1998 : In this study, we demonstrate that AKT2 is activated in response to stimulation by insulin in a dose- and time dependent manner in human ovarian carcinoma cells and that activation of AKT2 is abolished in cells pretreated with wortmannin, an inhibitor of phosphatidylinositol 3-kinase ( PI 3-kinase ) ... Collectively, these data indicate that activation of AKT2 by insulin is mediated by PI 3-kinase and that GSK-3 is a downstream target of AKT2, suggesting a potentially important role of AKT2 in glycogen synthesis and other GSK-3 signaling pathways
Zhande et al., J Biol Chem 2006 : We found that insulin induced ERK1/2 and Akt kinase activities were completely abolished 10 min after inhibition of the corresponding upstream kinases with PD98059 and LY294002, respectively ... In parallel experiments, insulin induced phosphorylation of Akt , ERK1/2, and insulin receptor substrate-1/2 was decreased and followed similar kinetics
Fukui et al., Diabetes 2005 : Insulin induced phosphorylation of Akt in liver was impaired in WT-SHIP2 expressing db/+m mice, whereas the reduced phosphorylation was restored in DeltaIP-SHIP2 expressing db/db mice
Yokota et al., Biochim Biophys Acta 1998 (Insulin Resistance) : In contrast, GLUT4 translocation remained unchanged for 2 h after insulin treatment, and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) also remained constant for up to 2 h. Chronic GH treatment had almost no effect on insulin stimulated Akt kinase activation and GLUT4 translocation
Bilim et al., Cardiovascular diabetology 2008 (Atrophy...) : Akt/PKB is associated with a downstream insulin signaling, and PKCbeta attenuates insulin stimulated Akt phosphorylation
Cui et al., Pancreas 2012 (Insulinoma) : Likewise, Akt inhibition also reduces both glucose stimulated and potassium depolarization stimulated insulin secretion from INS-1 cells
Diao et al., J Biol Chem 2005 : Defects in siRNA-IR expressing alpha-cells were associated with an alteration in the activity of Akt and p70S6K where insulin induced phosphorylation of protein kinase B/AKt was greatly reduced while p70S6K activation was enhanced, suggesting that the related pathways play important roles in alpha cell function
Su et al., J Biol Chem 2006 : Small interference RNA against a single Rab5 isoform had no effect on protein kinase B (PKB)/Akt or MAPK activation by insulin in NIH3T3 cells overexpressing human insulin receptor ... However, simultaneous knockdown of all three Rab5 isoforms dramatically attenuated PKB/Akt activation by insulin without affecting MAPK activation ... Down-regulation of GAPex-5 impaired insulin stimulated PKB/Akt activation
Garbow et al., Am J Physiol Gastrointest Liver Physiol 2011 (Fatty Liver...) : Ketogenic diet fed mice ultimately develop systemic glucose intolerance, hepatic endoplasmic reticulum stress, steatosis, cellular injury, and macrophage accumulation, but surprisingly insulin induced hepatic Akt phosphorylation and whole-body insulin responsiveness are not impaired
D'Alessandris et al., FASEB J 2004 : BADGP reversed the glucosamine induced reduction in insulin stimulated phosphorylation of IR, IRS-1, IRS-2, Akt , GSK-3, and FOXO1a
Hoene et al., J Physiol 2009 : The induction of endogenous insulin secretion by a glucose load directly after the exercise bout resulted in a significantly higher PKB/Akt phosphorylation in the liver of exercised mice
Butler et al., Diabetes 2002 : Transfection of cells in culture with ASO targeting PTEN reduced PTEN mRNA and protein levels and increased insulin stimulated Akt phosphorylation in alpha-mouse liver-12 ( AML12 ) cells ... Inhibition of PTEN expression also dramatically reduced insulin concentrations in ob/ob mice, improved the performance of db/db mice during insulin tolerance tests, and increased Akt phosphorylation in liver in response to insulin
Weigert et al., J Biol Chem 2005 : Unexpectedly, after acute insulin stimulation, we observed that phosphorylation of Ser ( 318 ) is not inhibitory but rather enhances insulin signal transduction because introduction of Ala ( 318 ) led to a reduction of the insulin stimulated Akt/protein kinase B phosphorylation
Yang et al., PloS one 2012 (Diabetes Mellitus, Type 2...) : Last, KD of 61 of the above 113 genes potentiated insulin stimulated Akt phosphorylation, suggesting that they suppress gluconeogenic gene by enhancing insulin signaling
Liu et al., Am J Physiol Endocrinol Metab 2009 (Insulin Resistance) : Increased basal level of Akt dependent insulin signaling may be responsible for the development of insulin resistance ... Together, our results indicate that increased basal Akt dependent insulin signaling suppresses mitochondrial production, increases ectopic fat accumulation, induces oxidative stress, and desensitizes insulin signaling in subjects with insulin resistance and hyperinsulinemia
Moreno-Navarrete et al., J Nutr Biochem 2011 (Inflammation) : In both subcutaneous and visceral preadipocytes, lactoferrin ( 1 and 10 µM ) increased adipogenic gene expressions and protein levels ( fatty acid synthase, PPAR?, FABP4, ADIPOQ, ACC and STAMP2 ) and decreased inflammatory markers ( IL8, IL6 and MCP1 ) dose-dependently in parallel to increased insulin induced ( Ser473 ) AKT phosphorylation
Bhavsar et al., Journal of cardiovascular translational research 2010 (Cardiomegaly) : Clenbuterol treated cultures also showed elevated insulin-like growth factor I (IGF-1) mRNA and activation of the protein kinase Akt
Ren et al., PloS one 2012 (Fatty Liver...) : Glucose intolerance ( iAUC increased by ~60 % ) and blunted insulin stimulated hepatic Akt and GSK3ß phosphorylation ( ~40-60 % ) were found in both feeding conditions ( p < 0.01 vs Con, assessed after 1 week )
Ceolotto et al., Free Radic Biol Med 2006 : Insulin induced Akt phosphorylation was increased by pravastatin and ERK1/2 phosphorylation attenuated
Smith , Int J Obes Relat Metab Disord 2002 (Diabetes Mellitus...) : In contrast, upstream insulin signaling in skeletal muscle from diabetic subjects only shows modest impairments and PKB/Akt activation in vivo by insulin appears normal
Hu et al., Mol Endocrinol 2012 : PPAR? overexpression more than doubled insulin stimulated thymoma viral proto-oncogene ( AKT ) phosphorylation during low lipid availability ... Furthermore, in myotubes exposed to palmitate levels that inhibit insulin signaling, PPAR? overexpression increased insulin stimulated AKT phosphorylation and glycogen synthesis over 3-fold despite simultaneously increasing myocellular palmitate uptake ... In vivo, PPAR? overexpression more than doubled insulin dependent AKT phosphorylation in lipid treated mice but did not augment insulin stimulated glucose uptake
Li et al., Hepatology 2011 (Diabetes Mellitus...) : In cultured hepatocytes, PANDER overexpression induced lipid deposition, increased FOXO1 expression, and suppressed insulin stimulated Akt activation and FOXO1 inactivation
Moreno et al., Age (Dordrecht, Netherlands) 2010 (Insulin Resistance) : In view of these findings, the purpose of the present study was to examine the role of chronic 17beta-estradiol treatment on insulin sensitivity during the aging process, and its effects on levels of the insulin-sensitive glucose transporter Glut4 ( both total and plasma membrane localized ), the interaction between p85alpha subunit of PI3-k and IRS-1, Tyr- and Ser-612 phosphorylation of IRS-1 levels, and Ser-473 phosphorylation of Akt
Kim et al., Mol Cell 2012 : Disruption of mTORC2 impairs the insulin induced activation of Akt , an mTORC2 substrate
Samane et al., Metabolism 2009 (Glucose Intolerance...) : Insulin induced phosphorylation of Akt and Erk in adipose tissues, skeletal muscles, and liver was greatly attenuated in HFHS rats as compared with chow fed controls
Takebayashi et al., Biochem Biophys Res Commun 2011 : The effects of RBP4 on nitric oxide ( NO ) and insulin stimulated endothelin-1 (ET-1) secretion and on phosphorylation ( p ) of Akt , endothelial NO synthetase (eNOS), and extracellular signal regulated kinase ( ERK ) 1/2 were investigated in bovine vascular aortic endothelial cells ( BAECs )
Luo et al., Mol Cancer Ther 2005 (Disease Progression...) : Consistent with data from knockout animals, the Akt inhibitors induce an increase in insulin secretion
Prudente et al., J Clin Endocrinol Metab 2009 (Diabetes Mellitus, Type 2) : TRIB3 inhibits insulin stimulated Akt phosphorylation and subsequent insulin action
Jones et al., Diabetes 2010 : Insulin increased AKT and insulin receptor substrate 1 (IRS-1) phosphorylation, system A activity, and SNAT2 expression
Onnockx et al., J Cell Physiol 2008 : Co-transfection of SHIP2 and APS in CHO-IR cells further increases the inhibitory effect of SHIP2 on Akt insulin induced phosphorylation
Carré et al., Endocrinology 2008 : In Grb14 depleted hepatocytes, insulin induced phosphorylation of Akt , and of its substrates glycogen synthase kinase 3 and fork-head box protein 1, was increased
Iwakami et al., PloS one 2011 : Treatment with high concentrations of H2O2 ( 25-50 µM ) for 3 h reduced insulin stimulated Akt phosphorylation, and increased the phosphorylation of both JNK and its substrate c-Jun
Marzban et al., Mol Cell Biochem 2001 (Body Weight...) : Insulin ( 5 U/kg, i.v. ) increased PKBalpha activity more than 10-fold and PKBbeta activity more than 3-fold in both animal models
Sargis et al., Biochim Biophys Acta 2012 (Insulin Resistance) : Treatment of primary murine adipose tissue in vitro with 100nM TF for 48h markedly attenuated acute insulin stimulated Akt phosphorylation in a strain- and species independent fashion ... A similar TF-induced reduction in insulin stimulated Akt phosphorylation was observed in primary human subcutaneous adipose tissue
Bridgewater et al., Kidney Int 2005 : IGF-1 stimulation resulted in the formation of the insulin receptor substrate (IRS)-1-p85 complex, an increase in PI3 kinase activity, and activation of protein kinase B ( AKT/PKB ) and the bcl-2 family member bad
Nomura et al., Biol Pharm Bull 2008 : Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin stimulated activation of Akt , a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin dependent translocation of a glucose transporter, ( GLUT)4, into the plasma membrane ... Although genistein, silybin, EGCG and theaflavins had no effect on the insulin stimulated activation of Akt , they blocked insulin dependent GLUT4 translocation
He et al., Mol Endocrinol 2006 (Insulin Resistance) : Insulin stimulated Akt phosphorylation and 2-deoxyglucose uptake were not inhibited only by IL-1alpha
Ballou et al., J Biol Chem 2001 : PE treatment does not activate phosphatidylinositol 3-kinase or Akt ( Ballou, L. M., Cross, M. E., Huang, S., McReynolds, E. M., Zhang, B. X., and Lin, R. Z. ( 2000 ) J. Biol. Chem. 275, 4803-4809 ), but instead inhibits insulin induced Akt activation and GSK-3beta phosphorylation ... One pathway inhibits insulin induced GSK-3beta phosphorylation by blocking insulin activation of Akt
Kovacic et al., J Biol Chem 2003 : In addition, insulin caused an increase in Akt phosphorylation and a decrease in AMPK phosphorylation at its major regulatory site ( threonine 172 of the alpha catalytic subunit )
Oiso et al., Biochem Biophys Res Commun 2011 : In HepG2 cells, insulin stimulated phosphorylation of Akt and forkhead box O 1 (FoxO1) was increased by Ky-2
Arellano-Plancarte et al., Biochem Pharmacol 2010 (Insulin Resistance) : To investigate the potential interactions between the angiotensin II (Ang II) and insulin signaling systems, regulation of IRS-1 phosphorylation and insulin induced Akt activation by Ang II were examined in clone 9 ( C9 ) hepatocytes ... Both inhibitors blocked the effect of Ang II on insulin induced activation of Akt
Mazière et al., Atherosclerosis 2004 : However, CuLDL dose-dependently prevented the INS signaling pathway, by inhibiting the INS induced phosphorylation of the signaling kinases ERK and PKB/Akt and the INS induced activation of the transcription factors AP1 and NFkappaB
Lamia et al., Mol Cell Biol 2004 : Furthermore, in vivo insulin induced activation of the protein kinase Akt is enhanced in skeletal muscle and liver from mice lacking phosphatidylinositol 5-phosphate 4-kinase beta
Lee et al., J Biol Chem 2003 : Reduced Ser ( 307 ) phosphorylation was directly related to increased insulin stimulated tyrosine phosphorylation, Akt phosphorylation, and glucose uptake
Pellegatta et al., J Cardiovasc Pharmacol 2006 : In human endothelial cells amino acids inhibit insulin induced Akt and ERK1/2 phosphorylation by an mTOR dependent mechanism ... Insulin induces the phosphorylation of Akt and extracellular signal regulated protein kinase ( ERK ) 1/2, whereas amino acids did not ... Insulin induced phosphorylation of Akt ( at 15 and 30 minutes ) is not accompanied by the phosphorylation of the downstream kinase p70/S6-K, indicating the existence of a negative feedback at this level
Dimatteo et al., Biochim Biophys Acta 2013 : As compared to untransfected cells, a progressive increase of ENPP1 inhibitory activity on insulin induced IR ß-subunit autophosphorylation and on Akt-S ( 473 ) phosphorylation was observed in ENPP1-3'myc, ENPP1-dI-3'myc and ENPP1-dII-3'myc cells
Zhou et al., J Biol Chem 2010 : A novel pleckstrin homology domain containing protein enhances insulin stimulated Akt phosphorylation and GLUT4 translocation in adipocytes ... Furthermore, adenovirus mediated expression of PHLDB1 in adipocytes enhanced insulin stimulated Akt and p70 S6 kinase phosphorylation, as well as GLUT4 translocation ... These results indicate that PHLDB1 is a novel modulator of Akt protein kinase activation by insulin
Tremblay et al., Diabetes 2003 (Obesity) : Dietary cod protein restores insulin induced activation of phosphatidylinositol 3-kinase/Akt and GLUT4 translocation to the T-tubules in skeletal muscle of high-fat fed obese rats ... The activation of the downstream kinase Akt/PKB by insulin , assessed by in vitro kinase assay and phosphorylation of GSK-3beta, were also impaired in muscle of high-fat fed rats consuming casein or soy protein, but these defects were also fully prevented by dietary cod protein
Jové et al., Endocrinology 2006 : Palmitate treatment enhanced the expression of phospho-PKCtheta, suggesting that this PKC isoform was involved in the changes reported, and coincubation of palmitate treated cells with the PKC inhibitor chelerythrine prevented the palmitate induced reduction in the expression of IkappaBalpha and insulin stimulated Akt activation
Dransfeld et al., Biochem J 2001 : However, inhibition of 12-LO did not affect the association of phosphatidylinositol 3-kinase with IRS-1 and the phosphorylation of Akt/protein kinase B in response to insulin
Chenal et al., Eur J Neurosci 2008 : Investigation of the putative signalling pathways leading to translation activation revealed that insulin and IGF-1 induced p44- and p42 MAPK, Akt and mTOR phosphorylation
Wang et al., Endocrinology 2008 (Obesity) : Evodiamine treatment also reduced insulin stimulated phosphorylation of Akt , a crucial regulator of adipocyte differentiation ; and the reduction of phosphorylated-Akt and augmentation of phosphorylated ERK were reversed by blockade of the MAPK kinase/MAPK signaling pathway, restoring adipogenesis in the cultures
Nakae et al., J Biol Chem 1999 : Because Akt is phosphorylated in response to insulin and has been implicated in a variety of insulin effects, we investigated whether insulin affects phosphorylation of FKHR
Oliveira et al., Am J Physiol Endocrinol Metab 2004 : Reduction of PGC-1alpha expression resulted in no modification of insulin induced tyrosine phosphorylation of the IR and Ser473 phosphorylation of Akt
Gaidhu et al., Mol Endocrinol 2010 : Subsequently, basal and insulin stimulated glucose uptake and the phosphorylation of AMPK, acetyl-CoA carboxylase, Akt , and the Akt substrate of 160 kDa ( AS160/TBC1D4 ) were determined ... AICAR increased AMPK activation without affecting basal and insulin stimulated Akt1/2 phosphorylation on Thr ( 308 ) and Ser ( 473 ) residues
Zhou et al., FEBS Lett 2007 (Insulin Resistance) : CM and resistin both induce insulin resistance with a robust decrease in insulin stimulated phosphorylation of Akt and GSK3
Zhou et al., Metabolism 2007 : Berberine did not induce Ser473 phosphorylation of Akt nor enhance insulin induced phosphorylation of Akt
Hitomi et al., Hypertension 2007 (Insulin Resistance) : Aldosterone treatment abolished insulin induced Akt phosphorylation ( 100 nmol/L ; 5 minutes ; n=4 )
Cheng et al., Proc Natl Acad Sci U S A 2012 (Diabetes Mellitus, Type 2) : Such changes are accompanied by diminished insulin stimulated Akt activation ... These findings demonstrate that APPL1 couples insulin stimulated Akt activation to GSIS by promoting the expression of the core exocytotic machinery involved in exocytosis and also suggest that reduced APPL1 expression in pancreatic islets may serve as a pathological link that couples insulin resistance to ß-cell dysfunction in type 2 diabetes
Kim et al., Arterioscler Thromb Vasc Biol 2008 (Body Weight...) : The early onset of vascular inflammation was accompanied by biochemical evidence of both endothelial dysfunction ( reduced nitric oxide production ; induction of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 ) and insulin resistance ( impaired insulin induced phosphorylation of Akt and eNOS )
Koh et al., Mol Cell Biol 2006 (Insulin Resistance) : MLKB1KO mice had increased insulin stimulated Akt phosphorylation and a > 80 % decrease in muscle expression of TRB3, a recently identified Akt inhibitor
Del Aguila et al., Am J Physiol Endocrinol Metab 2000 (Pain) : Insulin stimulated phosphatidylinositol (PI) 3-kinase, Akt ( protein kinase B ) serine phosphorylation, and Akt activity were reduced 34, 65, and 20 %, respectively, after ECC ( P < 0.05 )
Kobayashi et al., J Nutr Sci Vitaminol (Tokyo) 2012 (Body Weight...) : Coffee improves insulin stimulated Akt phosphorylation in liver and skeletal muscle in diabetic KK-A ( y ) mice ... Coffee ingestion significantly increased the insulin induced serine phosphorylation of Akt in liver and skeletal muscle, but not in epididymal fat, of KK-A ( y ) mice
Deng et al., Respir Res 2012 (Acute Lung Injury) : In vivo, insulin decreased TLW, enchanced AFC, increased the expressions of a-, ß-, and ?-ENaC and the level of phosphorylated Akt , attenuated lung injury and improved the survival rate in LPS induced ALI, the effects of which were blocked by wortmannin ... In vitro, insulin increased the expressions of a-, ß-, and ?-ENaC as well as the level of phosphorylated Akt but LY294002 and Akt inhibitor significantly prevented insulin induced increase in the expression of ENaC and the level of phosphorylated Akt respectively
de la Monte et al., Journal of population therapeutics and clinical pharmacology = Journal de la thérapeutique des populations et de la pharamcologie clinique 2010 (Insulin Resistance) : As a result, insulin activation of PI3K-Akt , which mediates neuronal survival, motility, energy metabolism, and plasticity, is impaired
van Dam et al., Mol Endocrinol 2005 : Strikingly, insulin stimulated Akt activity, but not phosphatidylinositol 3 kinase activity, was blocked at 19 C. Consistent with a multistep process in GLUT4 trafficking, insulin stimulated GLUT4 translocation could be primed by treating cells with insulin at 19 C, whereas this was not the case for Akt activation
Kohlhaas et al., Biochem Biophys Res Commun 2011 : Insulin rapidly stimulated L-arginine transport, an effect abrogated by incubation with inhibitors of phosphatidylinositol-3'-kinase or infection with adenoviruses expressing a dominant negative mutant Akt
Gonzalez et al., Proc Natl Acad Sci U S A 2009 : We found that insulin activates both Akt1 and Akt2 in adipocytes, but differentially regulates the subcellular distribution of these Akt isoforms
Grillo et al., Brain Res 2009 : Insulin stimulated phosphorylation of Akt and translocation of GLUT4 were blocked by pretreatment with the PI3-kinase inhibitor LY294002 ... Confocal immunofluorescence determined that insulin stimulated phosphorylation of Akt was localized to neurons and colocalized with the insulin receptor and GLUT4 in the rat hippocampus, thereby identifying the functional anatomical substrates of insulin signaling in the hippocampus
Senn et al., Diabetes 2002 (Insulin Resistance) : In addition, insulin dependent activation of Akt , important in mediating insulin 's downstream metabolic actions, is markedly inhibited by IL-6 treatment
Bartolomé et al., Endocrinology 2010 : The use of different beta-cell lines expressing or not the insulin receptor ( IR ( +/+ ) and IR ( -/- ) ) or with a reconstituted expression of IR isoform A or B ( Rec A and Rec B ) revealed that both phosphatidylinositol 3-kinase/Akt/TSC/mTOR complex 1 and MAPK kinase/ERK pathways mediate insulin signaling in IR ( +/+ ) -, IRA-, or IRB expressing cells ... The effect of insulin on Akt phosphorylation was completely inhibited by the use of the phosphatidylinositol 3-kinase inhibitor wortmannin in IR ( +/+ ) and Rec B cells, a partial inhibitory effect being observed in Rec A cell line
Mima et al., Kidney Int 2011 (Diabetes Mellitus, Experimental...) : Compared with nondiabetic and Zucker lean rats, the insulin induced phosphorylation of insulin receptor substrate-1 (IRS1), Akt , endothelial nitric oxide synthase, and glycogen synthase kinase 3a were selectively inhibited in the glomeruli but not in the renal tubules of both respective models
Cichy et al., J Biol Chem 1998 : Insulin lowers IGFBP-1 mRNA levels, inhibits IGFBP-1 promoter activity, and activates PKB/Akt in HepG2 hepatoma cells through a PI3K dependent, rapamycin-insensitive mechanism
Deshmukh et al., Mol Endocrinol 2008 : Insulin increased Akt Ser473 phosphorylation ( P < 0.01 ), irrespective of genotype or presence of AICAR
Liu et al., Exp Cell Res 2011 : Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors ... Insulin induced ERK and Akt activation , and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor
Ji et al., Curr Pharm Des 2013 : Accumulating evidence has suggested insulin induced PI3K-Akt-eNOS survival signaling as a potent therapeutic target for cardiovascular disorders and highlighted the impaired survival signaling as a key link between insulin resistance and cardiovascular disease
Batista et al., PloS one 2012 : This impairment was associated with a reduced insulin stimulated Akt phosphorylation in the Thr ( 308 ) residue
Akiba et al., Biochem Pharmacol 2004 : Although caffeine did not alter insulin induced activation of PI3K and protein kinase C-zeta (PKCzeta), an isoform of atypical PKC, which is reported to have an important role in insulin induced GLUT4 translocation, we found that insulin induced phosphorylation and activation of Akt were blocked by pre-treatment with caffeine
Oriente et al., J Biol Chem 2001 : PDK1 ( a phosphatidylinositol trisphosphate dependent kinase ) and Akt/protein kinase B (PKB) activation by insulin showed no difference in B2, F4, and in control L6hIR cells ... In L6hIR, inhibition of PKC zeta activity by either a PKC zeta antisense or a dominant negative mutant also reduced by 75 % insulin inactivation of GSK3 alpha and -beta ( p < 0.001 ) and insulin stimulation of GS ( p < 0.002 ), similar to Akt/PKB inhibition. In L6hIR, insulin induced protein kinase C zeta (PKC zeta) co-precipitation with GSK3 alpha and beta. PKC zeta also phosphorylated GSK3 alpha and -beta. Alone, these events did not significantly affect GSK3 alpha and -beta activities. Inhibition of PKC zeta activity, however, reduced Akt/PKB phosphorylation of the key serine sites on GSK3 alpha and -beta by > 80 % ( p < 0.001 ) and prevented full GSK3 inactivation by insulin
de Alvaro et al., J Biol Chem 2004 (Insulin Resistance) : Consequently, TNF-alpha, through activation of p38 MAPK and IKK, produces serine phosphorylation of IR and IRS-1, impairing its tyrosine phosphorylation by insulin and the corresponding activation of phosphatidylinositol 3-kinase and Akt , leading to insulin resistance on glucose uptake and GLUT4 translocation
Carvalho et al., Diabetologia 2000 (Diabetes Mellitus, Type 2) : Insulin increased protein kinase B/Akt translocation to the the plasma membrane about twofold [ ( p < 0.03 ) in non-diabetic cells but this effect was impaired in diabetic cells ( approximately 30 % ; p > 0.1 ) ] ... Furthermore, insulin stimulated translocation of protein kinase B/Akt to the plasma membrane, where serine phosphorylation and full activation occurs, is impaired in Type II diabetes
Steiler et al., Endocrinology 2003 (Diabetes Mellitus, Experimental...) : Under euglycemic and hyperglycemic conditions, basal and insulin stimulated action on phosphatidylinositol (PI) 3-kinase, protein kinase B/Akt , and ERK were reduced in GK rats, whereas insulin stimulated protein kinase C (PKC)zeta activity was not altered
Bonaventura et al., Life Sci 2013 (Insulin Resistance) : Skeletal muscle insulin sensitivity was assessed by in vivo insulin induced Akt phosphorylation ( Western blot )
Brozinick et al., Biochem J 1999 : Additionally, KN-62 affected neither insulin stimulated phosphoinositide 3-kinase nor Akt activity, suggesting that the effects of KN-62 are not due to non-specific effects of this inhibitor on these regions of the insulin signalling cascade
Liu et al., Eur J Haematol 2010 (Multiple Myeloma) : Baicalein had no effect on Akt phosphorylation induced by the insulin-like growth factor-1 (IGF-1) in NOP2 cells
Chen et al., J Cell Sci 2003 : Insulin does not further enhance the cell-surface level of HA-GLUT4-Akt2-wt , but does stimulate the translocation of HA-GLUT4-Akt2-KD
Schüppel et al., J Invest Dermatol 2008 : The inhibition of insulin mediated Akt activity by S1P is completely abolished in the presence of PKCdelta siRNA indicating that this isozyme is selectively potent at causing dephosphorylation of Akt and modifying keratinocyte proliferation
Gusinjac et al., Metabolism 2011 : Finally, studies on proadipogenic insulin signaling in ACLP overexpressing preadipocytes demonstrated that insulin stimulated Akt phosphorylation was significantly decreased by 27 % in cells cultured in collagen I-coated dishes vs standard dishes
Chen et al., J Appl Physiol 2005 (Prenatal Exposure Delayed Effects) : There was no significant difference in basal or insulin stimulated Akt activity between EtOH exposed rats and controls
Oshikawa et al., Proc Natl Acad Sci U S A 2004 (Insulin Resistance) : Insulin stimulated activation of insulin receptors and downstream molecules, such as IRS-1 and Akt , was attenuated in the skeletal muscles of Cav3 null mice, but not in the liver, without affecting protein expression or subcellular localization
Thompson et al., Mol Med 2008 (Hemorrhage...) : However, following hemorrhage, there was an almost complete loss of insulin induced Akt phosphorylation in triceps, and severely decreased tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1
Nazari et al., J Med Invest 2007 (MAP Kinase Signaling System) : Pretreatment of Ang II increased ERK1/2 phosphorylation and inhibited insulin induced Akt phosphorylation
Junkin et al., Am J Physiol Regul Integr Comp Physiol 2009 : Resistin acutely impaired insulin stimulated glucose transport and Akt phosphorylation, but only in the presence of palmitate, implicating a role for altered FA metabolism
Grote et al., Exp Diabetes Res 2011 (Diabetes Mellitus, Experimental...) : Additionally, Akt activation and neurite outgrowth in response to insulin were significantly decreased in DRG cultures from diabetic ob/ob mice
Sherwood et al., Am J Physiol 1999 : Differential regulation of MAP kinase, p70 ( S6K ), and Akt by contraction and insulin in rat skeletal muscle ... However, insulin , but not contraction, increased p70 ( S6K ) and Akt activities in the muscle
Dridi et al., Diabetes 2013 (Mucolipidoses) : Cells from sialidosis patients with a genetic deficiency of Neu1 show impairment of insulin induced phosphorylation of downstream protein kinase AKT , and treatment of these cells with purified Neu1 restores signaling
Botolin et al., J Lipid Res 2006 (MAP Kinase Signaling System) : 22 : 6,n-3 transiently inhibits insulin induced Akt phosphorylation but induces Erk phosphorylation
Krook et al., Diabetes 1997 (Diabetes Mellitus, Type 2...) : Improved glucose tolerance restores insulin stimulated Akt kinase activity and glucose transport in skeletal muscle from diabetic Goto-Kakizaki rats
Caperuto et al., Endocrine 2006 (Body Weight...) : However, IRS-3 association with PI(3)-kinase was reduced in both models, as well as insulin induced AKT and PKC phosphorylation
Okamoto et al., Diabetes 2007 : These data demonstrate that deletion of Trib3 has minimal effect on insulin induced Akt activation in hepatic tissue, and, as such, they question any nonredundant role for Trb3 in the maintenance of glucose and energy homeostasis in mice
Calera et al., J Biol Chem 1998 : Insulin increases the association of Akt-2 with Glut4 containing vesicles ... We confirmed co-localization of Akt-2 and Glut4 in the basal state by immunopurification of Glut4 vesicles, which exhibited a 5.5-fold increase in Akt-2 in response to insulin relative to the amount of Glut4
Lanuza-Masdeu et al., Diabetes 2013 (Glucose Intolerance...) : At the molecular level, JNK activation in ß-cells inhibited insulin induced Akt phosphorylation, pancreatic and duodenal homeobox 1 nucleocytoplasmic shuttling, and transcription of insulin-target genes
Galic et al., Mol Cell Biol 2005 : Whereas insulin induced phosphatidylinositol 3-kinase/Akt signaling was prolonged in both TCPTP-/- and PTP1B-/- immortalized mouse embryo fibroblasts ( MEFs ), mitogen activated protein kinase ERK1/2 signaling was elevated only in PTP1B-null MEFs
Yu et al., Acta Biochim Biophys Sin (Shanghai) 2006 : Insulin also strongly activated both PI3K and the downstream effector Akt
Park et al., Diabetes 2005 (Heart Diseases...) : Insulin stimulated cardiac glucose metabolism was significantly reduced after 1.5 weeks of high-fat feeding, and cardiac insulin resistance was associated with blunted Akt mediated insulin signaling and GLUT4 levels
Carranza et al., Am J Physiol Cell Physiol 2008 : Insulin caused a wortmannin-sensitive increase in Akt/protein kinase B ( Akt/PKB ) phosphorylation and a dose dependent translocation of Akt/PKB to the membrane fraction
Argentino et al., Horm Metab Res 2005 (Body Weight...) : We measured insulin stimulated phosphorylation of the IR and IRS-1, IRS-1-p85 association and Akt activation, and the abundance of the IR, IRS-1, p85, GLUT-4 and IGF-1 receptor in skeletal muscle
Taniguchi et al., Proc Natl Acad Sci U S A 2006 (Diabetes Mellitus...) : Although PI3K enzymatic activity is diminished in L-Pik3r1KO livers because of a reduced level of regulatory and catalytic subunits of PI3K, insulin stimulated Akt activity is actually increased
Yang et al., J Mol Cell Cardiol 2013 (Diabetes Mellitus, Type 2) : The goals of this study were to define sub-mitochondrial localization of the translocated Akt, to dissect the effects of insulin on Akt isoform translocation, and to determine the direct effect of mitochondrial Akt activation on Complex V activity in normal and diabetic myocardium
Brown et al., Am J Physiol Endocrinol Metab 2008 (Diabetes Mellitus, Type 2) : However, there was no decrease in glucose uptake following insulin exposure, and insulin stimulated phosphorylation of Akt was normal under these conditions
Jhala et al., Genes Dev 2003 (Diabetes Mellitus...) : As induction of IRS2by cAMP enhanced activation of the survival kinase Akt in response to insulin and IGF-1, our results demonstrate a novel mechanism by which opposing pathways cooperate in promoting cell survival
Prawitt et al., Exp Cell Res 2008 : Insulin sensitivity as measured by insulin induced phosphorylation of Akt and S6 ribosomal protein was also independent of rosiglitazone
Flati et al., Int J Immunopathol Pharmacol 2010 : Essential amino acids improve insulin activation of AKT/MTOR signaling in soleus muscle of aged rats
Kim et al., J Clin Invest 1999 (Diabetes Mellitus, Type 2...) : Insulin increased Akt1/2 activity 1.7- to 2 ... Insulin stimulated phosphorylation of Akt1/2 was normal in obese and diabetic subjects ... In lean subjects only, insulin stimulated Akt1/2 activity correlated with glucose disposal rate
Plastaras et al., Cancer Biol Ther 2008 (Gastrointestinal Neoplasms) : PI3K/Akt signaling is stimulated by insulin ... We evaluated the time course of Akt stimulation by insulin and found it overlapped with protection from apoptosis induced by TRAIL ( TNFalpha Related Apoptosis Inducing Ligand ) in cell lines
Hyvönen et al., Mol Cell Endocrinol 2010 (Proteinuria) : Overexpression of SHIP2 in cultured podocytes reduces Akt activation in response to insulin , and promotes apoptosis
Xue et al., J Biol Chem 2007 (Diabetes Mellitus, Experimental...) : Insulin stimulated phosphorylation of IR, IRS proteins, Akt/protein kinase B, glycogen synthase kinase 3beta, and p70 ( S6K ) was impaired in DHet mouse muscle and liver and was differentially improved by PTP1B deficiency
Altar et al., Biol Psychiatry 2008 (Neuroblastoma) : Insulin phosphorylated its receptor in the neuroblastoma cells but not in astrocytes and, like IGF-1, increased ERK1/2 and Akt phosphorylation
Nelson et al., Am J Physiol Endocrinol Metab 2002 (Insulin Resistance) : Acute insulin stimulation increased total PM-Akt about twofold after preincubation without insulin in low or high glucose ... Conclusions : chronic exposure to high glucose or insulin downregulates acute insulin stimulated Akt activation, acting synergistically distal to PI 3-kinase ... Maximal insulin activates more Akt than required for maximal glucose transport stimulation
Kitamura et al., Mol Cell Biol 1998 : A mutant Akt ( Akt-AA ) in which the phosphorylation sites ( Thr308 and Ser473 ) targeted by growth factors are replaced by alanine has now been shown to lack protein kinase activity and, when overexpressed in CHO cells or 3T3-L1 adipocytes with the use of an adenovirus vector, to inhibit insulin induced activation of endogenous Akt ... Insulin activation of p70 S6 kinase was inhibited by approximately 75 % in CHO cells and approximately 30 % in 3T3-L1 adipocytes, whereas insulin induced activation of endogenous Akt was inhibited by 80 to 95 %, by expression of Akt-AA
Li et al., Horm Metab Res 2008 : However, insulin stimulated phosphorylation of Akt and PKCzeta and GLUT4 translocation to the plasma membrane were reduced
Ovadia et al., J Biol Chem 2011 (Insulin Resistance...) : Cultured differentiated pre-adipocyte cell lines exposed to the NO donors S-nitrosoglutathione ( GSNO ) or S-nitroso-N-acetylpenicillamine exhibited diminished insulin stimulated phosphorylation of Akt but not of GSK3 nor of insulin stimulated glucose uptake
Thorell et al., Am J Physiol 1999 : Phosphorylation of Akt , a putative signaling intermediary for GLUT-4 translocation, was increased in response to insulin ( 640 % above rest ), exercise ( 280 % ), and exercise plus insulin ( 1,000 % )
Nelson et al., Biochem Soc Trans 2005 (Alzheimer Disease...) : Oxidized low-density lipoprotein inhibits insulin dependent phosphorylation of the signalling kinases ERK ( extracellular-signal regulated kinase ) and PKB/Akt
Li et al., Rejuvenation Res 2007 : Although LID mice displayed reduced whole body glucose clearance, cardiomyocytes from LID mice exhibited dramatically enhanced insulin stimulated phosphorylation of insulin receptor and Akt
García-San Frutos et al., Endocrinology 2007 (Body Weight...) : Hypothalamic insulin stimulated insulin receptor, GSK3, AKT , and p70S6K phosphorylation decreased with aging
Kusudo et al., Genes Cells 2011 (Obesity) : FABP3 may also contribute to AS160 phosphorylation by maintaining insulin dependent Akt activation in the cells under a lipotoxic condition
Li et al., Circ Res 2013 : Conclusions : Specific protein kinase C-ß2 activation in the endothelial cells caused dysfunction and accelerated atherosclerosis because of loss of insulin stimulated Akt/endothelial nitric oxide synthase activation and angiotensin induced increases in endothelin-1 expression
Wijesekara et al., J Biol Chem 2010 : Adiponectin induced ERK and Akt phosphorylation protects against pancreatic beta cell apoptosis and increases insulin gene expression and secretion
O' Neill , Exp Gerontol 2013 (Alzheimer Disease) : Therapeutic approaches targeted at normalizing signaling through either the neuronal PI3-kinase/Akt/mTOR pathway or its activation by insulin and IGF-1 have been shown to be protective against the development of AD pathology and cognitive decline in animal models of AD and some of these therapies are entering clinical trials in patients with the disease
Piccolo et al., Oncogene 2004 (Lung Neoplasms...) : Here we show that Ins ( 1,3,4,5,6 ) P5 inhibits the serine phosphorylation and the kinase activity of Akt/PKB
Cui et al., Mol Cell Biochem 2011 : Insulin- or serum induced stimulation of ERK was significantly suppressed by depletion of PI3K-C2a, whereas phosphorylation of IRS-1 and the stimulation of PKB/Akt by insulin were not affected ... Taken together, our data indicate that PI3K-C2a may be a crucial factor in the stimulation of ERK activity in response to serum or insulin, whereas it is less important for the stimulation of PKB/Akt activity in response to insulin
Serra et al., J Cell Physiol 2003 (Disease Models, Animal...) : At the molecular level, impaired activation of the IR/IRS/PI3K pathway and a significant decrease both in the levels and in insulin stimulated activation of the serine/threonine kinase Akt were observed
Khalid et al., Breast Cancer Res Treat 2010 (Body Weight...) : Similarly, there was no difference in basal or maximum insulin stimulated phosphorylation of IRS-1/2, Akt/PKB , or p70 S6K in tumor cell lysates from HFD and LFD groups
Fediuc et al., J Cell Physiol 2008 : These effects were accompanied by an increase in basal and insulin stimulated phosphorylation of Akt ( Thr308 ), Akt ( Ser473 ), and GSK3alpha/beta
Sequea et al., Mech Ageing Dev 2013 : Moderate calorie restriction ( CR ) can improve insulin stimulated Akt phosphorylation and glucose uptake in muscles from 24 month-old rats, but the specific Akt substrates linking CR-effects on Akt to glucose uptake and other cellular processes are uncertain
Clavreul et al., Arterioscler Thromb Vasc Biol 2006 (Insulin Resistance) : OxLDL transiently increased phosphorylation of Erk and Akt within 5 minutes, but 60 minutes later, resulted in decreased insulin induced Akt phosphorylation ... OxLDL increased the S-glutathiolation of p21ras, and adenoviral transfection with either a mutant p21ras ( C118S ) lacking the predominant site of S-glutathiolation or a dominant negative mutant restored insulin induced Akt phosphorylation
Andreozzi et al., Arterioscler Thromb Vasc Biol 2008 (Cardiovascular Diseases...) : TRIB3 inhibitory activity on insulin stimulated Akt phosphorylation and the amount of protein which was coimmunoprecipitable with Akt were significantly greater in QR- and RR- as compared to QQ- HUVECs
Kumashiro et al., Diabetes 2008 (Glucose Intolerance...) : Simultaneously, overexpression of SOD1 in db/db mice enhanced the inactivation of forkhead box class O1, another regulator of PGC-1alpha expression, without the changes of insulin induced Akt phosphorylation in liver
Appleman et al., Mol Cancer Res 2012 : Interestingly, we find that activation of PI3K/AKT signaling occurs downstream of MAP-ERK kinase ( MEK ), and is dependent on the autocrine activation of the insulin-like growth factor (IGF) receptor ( IGF1R ) by IGF2
Maeda et al., Transplant Proc 2004 (Cadaver) : Our results suggest that PI3-kinase/Akt activation by insulin or EGF is beneficial for islet beta cell protection
Wu et al., J Biol Chem 2004 : Insulin treatment induced p70S6K, mTOR, and Akt phosphorylation, effects that were completely prevented by the PI3K inhibitor, LY294002
Pinnamaneni et al., Diabetologia 2006 (Insulin Resistance...) : Insulin stimulated Akt activity and phosphorylation and 2-deoxyglucose uptake were reduced with SCD1 siRNA
Li et al., PloS one 2013 : In mice fed normal diet, peripheral nesfatin-1 significantly increased insulin stimulated phosphorylation of AKT in skeletal muscle, adipose tissue and liver ; similar effects were observed in skeletal muscle and adipose tissue in mice fed high fat diet ... In vitro studies showed that nesfatin-1 increased both basal and insulin stimulated levels of AKT phosphorylation in cells derived from skeletal muscle, adipose tissue and liver
Sugano et al., J Neurochem 2006 : Enhancement of insulin induced PI3K/Akt/GSK-3beta and ERK signaling by neuronal nicotinic receptor/PKC-alpha/ERK pathway : up-regulation of IRS-1/-2 mRNA and protein in adrenal chromaffin cells ... Thus, stimulation of nAChRs up-regulated expression of IRS-1/IRS-2 via Ca ( 2+ ) -dependent sequential activation of cPKC-alpha and ERK, and enhanced insulin induced PI3K/Akt/GSK-3beta and ERK signaling pathways
Toschi et al., Mol Cell Biol 2009 : Suppression of PLD also blocked insulin stimulated Akt phosphorylation at Ser473 and the mTORC2 dependent phosphorylation of PRAS40
Dietze et al., Int J Obes Relat Metab Disord 2004 (Insulin Resistance) : Adipocyte conditioned medium strongly inhibited insulin induced serine phosphorylation of Akt in myocytes with a rapid parallel activation of the nuclear factor kappaB pathway in these cells
Descamps et al., J Immunol 2004 (Multiple Myeloma) : We show that Akt activation in response to insulin-like growth factor-1 (IGF-1) is highly variable from one human myeloma cell line to another one
Huang et al., J Biomed Sci 2009 (Cardiac Output, Low...) : Impairment of insulin stimulated Akt/GLUT4 signaling is associated with cardiac contractile dysfunction and aggravates I/R injury in STZ-diabetic rats ... Our results indicate that cardiac contractile dysfunction caused by a defect in insulin stimulated Akt/GLUT4 may be a major reason for the high mortality rate in I/R injured diabetic rats
Mori et al., Mol Cell Endocrinol 2005 : In spite of these differences, both FL-Grb10 and the BPS-SH2 fragment inhibited insulin stimulated phosphorylation of IRS1, IRS2, Akt/PKB , Shc, ERK1/2, APS, and c-Cbl to a similar extent
Jensen et al., PloS one 2008 (MAP Kinase Signaling System) : We conclude that altered insulin activation of the PI3K/Akt but not the MAPK pathway precedes and may contribute to development of whole-body insulin resistance and type 2 diabetes in men with LBW
Wang et al., Mol Cell Biol 2007 (Body Weight) : Loss of Grb10 expression in insulin target tissues, such as skeletal muscle and fat, resulted in enhanced insulin stimulated Akt and mitogen activated protein kinase phosphorylation
Brutman-Barazani et al., J Cell Biochem 2012 : Suppression of PKCd expression by transfection with RNAi, or overexpression of kinase dead ( dominant negative ) PKCd reduced both the insulin induced activation of PKB/Akt and the phosphorylation of glycogen synthase kinase 3 ( GSK3 ) and reduced significantly insulin induced glucose uptake
Jiang et al., J Biol Chem 2003 (Insulin Resistance) : The results showed that both PMA and TNFalpha inhibited insulin induced Akt phosphorylation and promoted IRS1 phosphorylation on Ser-307
Tatarczyk et al., Mol Cell Endocrinol 2011 (Fatty Liver...) : Accordingly, insulin induced inhibition of glycogen synthase phosphorylation as well as insulin induced GSK-3 and AKT phosphorylation were reduced by TGRL
Tsuchiya et al., Cell Metab 2012 (Atherosclerosis) : Paradoxically, the atheroprotective effect of FoxO deletion is associated with a marked decrease of insulin dependent Akt phosphorylation in endothelial cells, owing to reduced FoxO dependent expression of the insulin receptor adaptor proteins Irs1 and Irs2
Lim et al., PloS one 2009 (Insulin Resistance) : It also suppressed the insulin mediated phosphorylation of Akt
Anilkumar et al., Arterioscler Thromb Vasc Biol 2008 : After angiotensin II or TNFalpha treatment, JNK activation was augmented in Nox2 but not Nox4 transfected cells, whereas insulin augmented phosphorylation of p38MAPK, Akt , and GSK3beta specifically in Nox4 overexpressing cells and JNK specifically in Nox2 overexpressing cells
Vahsen et al., Horm Metab Res 2006 (Insulin Resistance) : Insulin regulated serine phosphorylation of Akt and GSK3alpha and GSK3beta was unaltered in heart and skeletal muscle of knockout mice, suggesting unaltered insulin signaling
Dietze-Schroeder et al., Diabetes 2005 (Insulin Resistance) : Human skeletal muscle cells cocultured with adipocytes or treated with adipocyte conditioned medium showed an impaired Akt and glycogen synthase kinase 3 serine phosphorylation in response to insulin ... Further, adipocyte conditioned medium generated in the presence of gAcrp30 was unable to perturb insulin stimulated Akt phosphorylation
Chen et al., Science signaling 2013 : However, insulin induced phosphorylation of AKT at Ser ( 473 ) was not impaired in Bmx knockout MEFs or liver tissue from Bmx knockout mice, which also showed increased insulin stimulated glucose uptake, possibly because of decreased abundance of the phosphatase PHLPP ( PH domain leucine-rich repeat protein phosphatase )
Sun et al., J Pharmacol Exp Ther 2007 (Hypertension...) : In lean SHR adipocytes, Akt activation by 100 nM insulin peaked at 3 min at 25-fold, whereas SHROB adipocytes showed only 4-fold activation
Deng et al., Am J Physiol Heart Circ Physiol 2007 (Cardiomyopathies...) : Insulin stimulated cardiac glucose uptake was significantly reduced after 15 wk of HCF feeding, and cardiac insulin resistance was associated with blunted Akt mediated insulin signaling along with glucose transporter GLUT4 translocation
Witczak et al., Diabetes 2007 : Akt ( Thr ( 308 ) ) phosphorylation was not altered by CaMKKalpha, and caCaMKKalpha plus insulin stimulation did not increase the insulin induced phosphorylation of Akt ( Thr ( 308 ) )
Ibrahim et al., PloS one 2011 (Body Weight...) : In addition, the ability of insulin to stimulate Akt phosphorylation and muscle glucose uptake was impaired in mice fed farmed salmon
Eguchi et al., Mol Cell Endocrinol 2007 : However, the expected functional consequences were not observed, as we saw no change in basal or insulin stimulated glucose uptake and phosphorylation of GSK3beta, Akt ( T308 and S473 ) or ERK1/2
Kandadi et al., J Inorg Biochem 2011 (Insulin Resistance) : Treatment of cultured, differentiated myotubes with palmitic acid evoked insulin resistance as evidenced by lower levels of insulin stimulated Akt-phosphorylation , elevated JNK-phosphorylation, ( assessed by Western blotting ), attenuation of phosphoinositol-3-kinase activity ( determined in the insulin-receptor substrate-1-immunoprecipitates by measuring the extent of phosphorylation of phosphatidylinositol by ?- ( 32 ) P-ATP ), and impairment in cellular glucose up-take, all of which were inhibited by Cr ( d-Phe ) ( 3 )
Nagira et al., Endocrinology 2006 (Second Messenger Systems) : Membrane-impermeable E2, E2-BSA, did not affect the insulin induced phosphorylation of Akt at 10 ( -8 ) m, but inhibited it at 10 ( -5 ) m
Zhang et al., Histochem Cell Biol 2010 : The results demonstrated that 5 microg/ml insulin promotes the phosphorylation of Akt and the primordial follicular assembly and activation process via the InsR/PI3K/Akt signaling pathway in the 16.5 dpc fetal mouse ovaries cultured in vitro ... However, the presence of 5 microg/ml insulin represses the phosphorylation of Akt and the follicular assembly and activation process in the 3 dpp mouse ovaries cultured in vitro
Symons et al., Circ Res 2009 (Disease Models, Animal...) : Basal and insulin mediated phosphorylation of extracellular signal regulated kinase 1/2 and Akt in the vasculature was preserved, but basal and insulin stimulated eNOS phosphorylation was abolished in vessels from HF versus lean mice
Long et al., Am J Physiol Endocrinol Metab 2003 : Insulin significantly enhanced the phosphorylation of Akt ( P < 0.03 ), 4E-BP1 ( P = 0.003 ), and p70 ( S6K ) ( P < 0.002 ) in ADX but not in Sham rats ... Glucocorticoid replacement blunted the effect of insulin on Akt , 4E-BP1, and p70 ( S6K ) phosphorylation and protein synthesis
Yang et al., J Mol Cell Cardiol 2009 (Diabetes Mellitus, Experimental...) : Insulin stimulates Akt translocation to mitochondria : implications on dysregulation of mitochondrial oxidative phosphorylation in diabetic myocardium ... Acute insulin stimulation induced phosphorylation of Akt and translocation of Akt to mitochondria in myocardium ... In vivo inhibition of Akt blocked insulin stimulation of phospho-Akt translocation and blunted activation of complex V. Insulin activated Akt translocation to mitochondria in cardiac muscle is a novel paradigm that may have important implications on myocardial bioenergetics
Park et al., Endocrinology 2008 (Body Weight...) : Leptin enhanced insulin signaling by potentiating IRS2 -- > Akt pathways, whereas resistin activated Akt without augmenting insulin receptor substrate 2 phosphorylation
Liang et al., PloS one 2013 : This inflammatory response led to reduced insulin stimulated IRS-1, Akt and AS160 phosphorylation and impaired glucose transport
Min et al., Int J Obes Relat Metab Disord 2013 (Obesity) : We then examined whether CPE regulates insulin receptor (IR) , a common upstream regulator of ERK and Akt
Yanai et al., Invest Ophthalmol Vis Sci 2002 : Of the 11 growth factors examined, platelet derived growth factor, insulin , insulin-like growth factors-1 and -2, and epidermal growth factor, each stimulated the proliferation of corneal fibroblasts, induced the activation of Akt in these cells, and protected them from apoptosis induced by sodium nitroprusside ( SNP )
Zhou et al., Diabetes Metab 2012 (Insulin Resistance...) : NOD1 activation weakened insulin signal transduction as revealed by increased JNK and IRS-1 Ser307 phosphorylation, inhibited IRS-1 tyrosine phosphorylation, and reduced insulin induced phosphorylation of Akt on Ser473 and Thr308 in human adipocytes
Moschella et al., Cell Signal 2013 : Silencing the expression of Rictor ( rapamycin-insensitive companion of mTOR ), an mTORC2 component, with a sh-RNA in cardiomyocytes lowers both insulin stimulated Akt and PKCe phosphorylation ... Additionally, expression of DN-PKCe significantly lowered the insulin stimulated Akt S473 phosphorylation, indicating an upstream role for PKCe in the Akt activation
Ido et al., Diabetes 2002 (Hyperglycemia) : In addition, the phosphorylation of Akt in the presence of 150 microU/ml insulin was impaired ... The results indicate that alterations in fatty-acid metabolism, impaired Akt activation by insulin , and increased caspase-3 activity precede visible evidence of apoptosis in HUVEC incubated in a hyperglycemic medium
Larsen et al., Adv Exp Med Biol 2013 (Body Weight) : Neither a high-fructose diet nor taurine supplementation induced significant changes in body weight, body fat or total calorie intake, fasting insulin levels, HOMA-IR, or insulin induced Akt phosphorylation in skeletal muscle.Fructose alone caused a decrease in liver triglyceride content, with taurine supplementation preventing this
Mariappan et al., J Biol Chem 2008 (Diabetes Mellitus, Type 2...) : High glucose and high insulin augmented activation of Akt , Erk, and p70S6 kinase
Jiang et al., J Biol Chem 2003 : The importance of PI 3-kinase-Akt pathway on VEGF expression was confirmed in mouse aortic smooth muscle cells isolated from insulin receptor substrate -1 knockout ( IRS-1-/- ) mice that showed parallel reductions of 46-49 % in insulin stimulated VEGF expression and PI 3-kinase-Akt activation ... Insulin induced activation of PI 3-kinase-Akt on hypoxia induced VEGF expression and neovascularization was reduced by 40 % in the retina of neonatal hypoxia model using IRS-1-/- mice
Wang et al., J Biol Chem 2007 : We found that treating C2C12 myotubes with adiponectin or rapamycin enhanced the ability of insulin to stimulate IRS-1 tyrosine phosphorylation and Akt phosphorylation, concurrently with reduced p70 S6 kinase phosphorylation at Thr389 as well as IRS-1 phosphorylation at Ser302 and Ser636/639 ... Rapamycin, but not adiponectin, enhanced insulin stimulated Akt phosphorylation in HeLa cells, which lack LKB1, and exogenous expression of LKB1 in HeLa cells rescued the insulin sensitizing effect of adiponectin
Morino et al., Diabetes 2008 (Insulin Resistance) : Furthermore, Tg IRS-1 Ser -- > Ala mice displayed a significant increase in insulin stimulated IRS-1 associated phosphatidylinositol 3-kinase activity and Akt phosphorylation in skeletal muscle in vivo compared with WT control littermates
De Souza et al., J Physiol 2010 (Diabetes Mellitus...) : Acute exercise improved insulin signalling, increasing insulin stimulated Akt and Foxo1 phosphorylation and decreasing HNF-4alpha protein levels in the liver of DIO and ob/ob mice under fasting conditions
Liu et al., Mol Cell Biol 2011 : Furthermore, we showed that the insulin receptor substrate 1 (IRS-1) expression and insulin induced Akt phosphorylation were significantly decreased as the result of activation of the S6K dependent negative feedback loop in PHLPP knockdown cells
Shen et al., Scientific reports 2013 : Upon insulin activation of cellular Akt , the enzyme multi phosphorylated a single serine residue of a diserine DCF substrate in a time dependent manner, culminating in monophospho- to triphospho-serine products
Keung et al., Diabetes 2013 (Glucose Intolerance...) : In the gastrocnemius muscle, oxfenicine increased pyruvate dehydrogenase activity, membrane GLUT4 content, and insulin stimulated Akt phosphorylation
Waraich et al., J Biol Chem 2008 : Moreover, both active PKC-delta and phosphorylation of Ser ( 357 ) were shown to be necessary for the attenuation of insulin stimulated Akt phosphorylation
Takata et al., J Biol Chem 1999 : A mutant Akt ( Akt-AA ) in which the phosphorylation sites targeted by growth factors are replaced by alanine was shown to inhibit insulin induced activation of both Akt and glycogen synthase in L6 myotubes ... Expression of a mutant Akt in which Lys179 in the kinase domain was replaced by aspartate also inhibited insulin induced activation of glycogen synthase but had no effect on insulin activation of endogenous Akt ... These data suggest that Akt , but not PKClambda, is required for insulin activation of glycogen synthase and for insulin induced phosphorylation of 4E-BP1
Märker et al., Diabetes 2012 (Inflammation...) : Hsp60 activated extracellular signal related kinase ( ERK ) -1/2, Jun NH ( 2 ) -terminal kinase ( JNK ), p38, nuclear factor ( NF ) -?B, and impaired insulin stimulated Akt phosphorylation in adipocytes
Adams et al., Diabetes 2004 (Hyperinsulinism...) : Stimulation of Akt phosphorylation by insulin in the obese subjects was significantly reduced after 30 min ( 0.96 +/- 0.11 vs. 1.84 +/- 0.38 arbitrary units ) or 45-60 min ( 0.68 +/- 0.17 vs. 1.52 +/- 0.26 ) of insulin infusion ( P < 0.05 for both )
Fujita et al., J Cell Biochem 2004 : Pretreatment with 10 ( -8 ) M DEX for 1 day inhibited insulin induced Akt phosphorylation, but not ERK1/2 phosphorylation, in ATDC5 cells
Xiong et al., BMB Rep 2009 : Insulin induced phosphorylation of Akt ( protein kinase B ) and GSK-3beta ( Glycogen synthase kinase ), subsequent dephosphorylation of glycogen synthase and glycogen synthesis were increased by inhibiting the expression of SKIP, whereas the insulin induced glycogen synthesis was decreased by overexpression of WT-SKIP
Miyagi et al., Mol Carcinog 2004 (Cell Transformation, Neoplastic...) : Chronic expression of RET/PTC 3 enhances basal and insulin stimulated PI3 kinase/AKT signaling and increases IRS-2 expression in FRTL-5 thyroid cells ... RET/PTC3 cells demonstrated higher basal and insulin stimulated levels of activated Akt , both of which were reduced by LY294002, a PI3 kinase inhibitor, but not PD98059, a MEK inhibitor
Ruan et al., Phytomedicine 2012 (Diabetes Mellitus, Type 2...) : Combined treatment of a low dose borapetoside C ( 0.1mg/kg, twice daily ) plus insulin for 7 days enhanced insulin induced IR and Akt phosphorylation and GLUT2 expression in the liver of T1DM mice
Takahashi et al., J Biol Chem 2003 : In bovine aortic endothelial cells ( BAECs ), the effects of vascular endothelial growth factor ( VEGF ) and insulin on eNOS-HSP90-Akt complex formation and eNOS activation were compared ... GA prevented insulin induced association of HSP90, Akt and CaM with eNOS and inhibited eNOS activation in BAECs ... Both platelet derived growth factor ( PDGF ) and insulin induced activation of Akt in BAECs, but only insulin caused HSP90-Akt-eNOS association and eNOS phosphorylation
Ijuin et al., Mol Cell Biol 2003 : In contrast, downregulation of intracellular SKIP levels by antisense oligonucleotides dramatically enhanced Akt ( protein kinase B ) phosphorylation in response to insulin , suggesting that endogenous SKIP downregulates insulin signaling
Morino et al., PloS one 2008 (Hyperglycemia...) : Because insulin resistance is characterized by a marked reduction in insulin stimulated PI3K mediated activation of Akt , we asked whether MES could increase Akt phosphorylation and ameliorate insulin resistance
Sasaoka et al., J Biol Chem 2004 : SH2 containing inositol phosphatase 2 predominantly regulates Akt2 , and not Akt1, phosphorylation at the plasma membrane in response to insulin in 3T3-L1 adipocytes ... Insulin induced phosphorylation of Akt , one of the molecules downstream of PI3-kinase, was inhibited by expression of wild-type SHIP2, whereas it was increased by expression of 5'-phosphatase-defective ( DeltaIP ) SHIP2 in whole cell lysates ... Thus, insulin induced phosphorylation of Akt2 at the PM was predominantly regulated by SHIP2, whereas the phosphorylation of Akt1 was only minimally affected ... Furthermore, insulin induced phosphorylation of Akt was effectively regulated by SHIP2 in embryonic fibroblasts derived from knockout mice lacking either insulin receptor substrate-1 or insulin receptor substrate-2 ... These results indicate that insulin specifically stimulates the redistribution of SHIP2 from the cytosol to the PM independent of 5'-phosphatase activity, thereby regulating the insulin induced translocation and phosphorylation of Akt2 at the PM
Summers et al., Mol Cell Biol 1998 : Regulation of insulin stimulated glucose transporter GLUT4 translocation and Akt kinase activity by ceramide
Leibiger et al., FASEB J 2010 : Hence, our results identify signal transduction via PI3K-C2alpha as a novel pathway whereby insulin activates PKB/Akt and thus discloses PI3K-C2alpha as a potential drugable target in type 2 diabetes
Sharma et al., Cardiovasc Res 2007 (Hypertension...) : Hypertensive patients with high plasma insulin or metabolic syndrome have a greater occurrence of LVH, which could be due to insulin activation of the serine-threonine kinase Akt and its downstream targets in the heart, resulting in cellular hypertrophy
Lynn et al., J Investig Med 2004 : Insulin stimulated Akt phosphorylation, eNOS phosphorylation, and NO production ... The phosphatidylinositol-3 kinase inhibitor wortmannin attenuated insulin stimulated Akt activation and NO production ... Treatment with the omega-3 fatty acid 20 : 5, but not 18 : 1, enhanced insulin stimulated NO production but failed to alter insulin stimulated Akt activation or eNOS serine 1179 phosphorylation
Liu et al., Biochem Biophys Res Commun 2000 (MAP Kinase Signaling System) : Insulin activation of mitogen activated protein ( MAP ) kinase and Akt is phosphatidylinositol 3-kinase dependent in rat adipocytes ... Insulin induced phosphorylation of AKT on serine/threonine residues, and its effect could be blocked by PI3 kinase inhibitors
Comellas et al., J Cell Sci 2010 : Insulin induced Akt activation is necessary and sufficient to promote Na ( + ) /K ( + ) -ATPase translocation to the plasma membrane
Omata et al., Endocr J 2005 : On the other hand, mastoparan at a lower concentration ( 15 microM or below ), which showed an insignificant effect on LDH release, potentiated the insulin action on glucose transport and Akt phosphorylation in the presence of adenosine deaminase
Viardot et al., Diabetes Metab Res Rev 2012 (Diabetes Mellitus, Type 2...) : Lymphocytes from obese subjects showed reduced insulin stimulated AKT-phosphorylation in vitro