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

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INS — PIK3CA

Pathways - manually collected, often from reviews:

Text-mined interactions from Literome

Pham et al., Circ Res 2000 : Insulin or H ( 2 ) O ( 2 ) increased the phosphorylation ( activation ) of PKB through PI3K , but, whereas insulin induced a sustained response, the response to H ( 2 ) O ( 2 ) was transient
Goetze et al., Biochem Biophys Res Commun 2001 : Insulin induced rapid tyrosine-phosphorylation of the IR and IRS-1 and caused a 2.8-fold increase of IRS-1 bound PI3K ... TNFalpha had no effect on insulin induced tyrosine-phosphorylation of IR or IRS-1, but inhibited insulin stimulated IRS-1/PI3K-association by 84 %
Théberge et al., Arch Biochem Biophys 2003 : These data indicate that prolongation of insulin stimulated ERK 1/2 and PI3-K activation by VS is due to a more stable complex formation of IRS-1 with the p ( 85 alpha ) subunit which may, in turn, be responsible for its ability to enhance and extend the biological effects of insulin
Safi et al., Mol Cell Biol 2004 : Activation of PI3-K by insulin or expression of an active form of PI3-K p110 induces a rapid translocation of CKIP-1 to the plasma membrane
Herbert et al., J Biol Chem 2000 : Phosphatidylinositol 3-kinase and protein kinase B were activated by insulin but not by TPA
Standaert et al., Endocrinology 2002 : The thiazolidenedione, rosiglitazone, increases basal and/or insulin stimulated glucose transport in various cell types by diverse but uncertain mechanisms that may involve insulin receptor substrate (IRS)-1 dependent PI3K ... Additionally, rosiglitazone increased IRS-1 and IRS-2 levels, thereby enhancing insulin effects on IRS-1- and IRS-2 dependent PI3K and downstream signaling factors PKC-lambda and protein kinase B
El-Kholy et al., FASEB J 2003 : Western blotting confirmed the specific inhibitory effects of LY294002 and wortmannin on insulin stimulated PI3K activity
Zhou et al., Vasc Med 2012 (Cardiovascular Diseases...) : Angiotensin ( Ang ) II inhibits insulin mediated PI3K pathway activation, thereby impairing endothelial NO production and Glut-4 translocation in insulin-sensitive tissues, which results in vascular and systemic insulin resistance, respectively
Sidhu et al., Mol Pharmacol 2001 : We investigated the dose dependence for this response and for the effects of insulin and extracellular matrix on PI3K signaling and CYP2E1 mRNA expression levels using a highly defined rat primary hepatocyte culture system
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
Yaspelkis et al., Life Sci 2004 : Leptin appeared to mediate these effects by normalizing insulin stimulated PI3-K activation and GLUT4 protein concentration in the RG
Yang et al., Life Sci 2008 : PI3K-GSK3beta signaling may be responsible for insulin stimulation of ET-1 production associated with insulin resistance and hyperinsulinemia
Aquila et al., J Clin Endocrinol Metab 2005 : In uncapacitated sperm, both insulin and leptin increased PI3K activity, Akt S473, and glycogen synthase kinase-3 S9 phosphorylation
Zhang et al., Am J Physiol Cell Physiol 2009 (Diabetes Mellitus...) : BLX-1002, a novel thiazolidinedione with no PPAR affinity, stimulates AMP activated protein kinase activity, raises cytosolic Ca2+, and enhances glucose stimulated insulin secretion in a PI3K dependent manner
Kim et al., Diabetes 2003 (Diabetes Mellitus...) : Insulin stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation and PI3K activity are impaired 40-50 % in diabetic subjects compared with lean or obese subjects
Al-Rasheed et al., J Am Soc Nephrol 2006 (Diabetic Nephropathies) : Phosphatidylinositol 3-kinase but not extracellular signal regulated mitogen activated protein kinase mediated C-peptide and insulin activation of NF-kappaB
Loh et al., Diabetologia 2012 (Diabetes Mellitus, Type 2...) : 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
Niswender et al., J Histochem Cytochem 2003 : We conclude that immunocytochemical PIP3 staining can detect changes in PI3K activation induced by insulin and leptin in cell culture and intact liver
Sbrissa et al., Mol Cell Endocrinol 2001 : Insulin but not PDGF or EGF stimulation of 3T3-L1 adipocytes markedly increased the PtdIns 3-P production ( 4.2-fold ) in PIKfyve immune complexes, primarily as a result of increased PI 3-K intrinsic enzymatic activity ... Intriguingly, while both insulin and PDGF caused an increase of class I ( A ) PI 3-K activity co-immunoprecipitated with tyrosine phosphorylated proteins, only insulin treatment yielded an activation of class I(A) PI 3-K in PIKfyve immune complexes
Listov-Saabye et al., J Appl Toxicol 2009 (Adenocarcinoma...) : Also, PI3K pathway activation by insulin was enhanced on a collagen IV surface
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 ... These results indicate that both PI3K and ROS independently regulated Akt signaling related, mercury induced insulin secretion inhibition
Lalioti et al., Proc Natl Acad Sci U S A 2009 : Insulin activation of Cdk5 requires PI3K signaling
Kosaki et al., J Biol Chem 1998 : The specific activity of the PI3K in the former was approximately half of that in the latter, suggesting that 14-3-3beta protein bound to IRS-1 inhibits insulin stimulated lipid kinase activity of PI3K in 3T3L1 adipocytes
Cui et al., Mol Endocrinol 2002 : We demonstrated that insulin mediated insulin receptor substrate (IRS)-2 associated PI3K activity was inhibited by AT2 receptor stimulation, whereas IRS-1 associated PI3K activity was not significantly influenced ... 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
Endo et al., Cancer Res 2007 : IGFs and insulin enhanced the endoplasmic reticulum ( ER ) stress response as monitored by induction of the CCAAT/enhancer binding protein homologous protein ( CHOP ) proteins and the X box protein-1 splicing under hypoxic conditions, and this response was suppressed by inhibiting PI3K and mTOR activity
Cheatham et al., Mol Cell Biol 1994 : Phosphatidylinositol 3-kinase ( PI 3-kinase ) is stimulated by insulin and a variety of growth factors, but its exact role in signal transduction remains unclear
Aoki et al., Am J Physiol Endocrinol Metab 2009 : In the livers of p85alpha-deficient mice, p50alpha played a compensatory role in insulin stimulated PI3K activation by binding to insulin receptor substrate (IRS)-1/2 ... The absence of an increase in insulin stimulated PI3K activation in the liver of p85alpha-deficient mice, unlike the muscles, may be associated with the molecular balance between the regulatory subunit and the catalytic subunit of PI3K
Nevzorova et al., Br J Pharmacol 2006 : The PI3K inhibitor, LY294002 ( 1 microM ), inhibited insulin- ( 174.9+/-5.9 to 142.7+/-2.7 % ) and zinterol- ( 166.9+/-7.6 to 141.1+/-8.1 % ) but not 8 Br-cAMP stimulated GU
Kim et al., Diabetes 2000 (Obesity) : In adipose tissue of obese rats, in spite of an 86 % reduction in insulin stimulated PI3K activity, activation of Akt2 was increased
Choi et al., J Clin Invest 2007 (Insulin Resistance...) : Insulin resistance in these tissues was associated with reduced insulin stimulated insulin receptor substrate 1- (IRS-1-) and IRS-2 associated PI3K activity in muscle and liver, respectively
Klein et al., Mol Endocrinol 2000 : Beta3-adrenergic stimulation also activated mitogen activated protein ( MAP ) kinase by 3.5-fold and caused a decrease in basal phosphoinositide (PI) 3-kinase activity detected in p110gamma- and Gbeta-subunit-immunoprecipitates in a time dependent manner, whereas insulin stimulated p110alpha- and phosphotyrosine associated PI 3-kinase activity
Xu et al., Yao Xue Xue Bao 2011 (Diabetes Mellitus, Experimental) : The result showed that insulin in combination with selenium could significantly lower blood glucose and blood lipid levels and markedly restored the PI3K and GLUT4 levels in cardiac muscle
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
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
Bhanot et al., Am J Physiol 1999 (Hyperinsulinism...) : Basal and insulin activated PI3K activities were further enhanced up to 2-fold and 1.3-fold, respectively, in FF rats
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
Kruszynska et al., J Clin Endocrinol Metab 2002 (Insulin Resistance) : The insulin induced increase in IRS-1 associated PI3K activity was impaired by elevated NEFA, so that activity at the end of the clamps with Intralipid was 35 % lower than in the control clamps ( P < 0.05 )
Orme et al., Nat Cell Biol 2006 : The Drosophila class I PI(3)K , Dp110, is activated by nutrient-responsive insulin signalling and modulates growth, oogenesis and metabolism ... Furthermore, insulin can not maximally activate PI(3)K signalling in Dp110 ( RBD ) imaginal discs and Dp110 ( RBD ) flies are small
Klöckener et al., Nat Neurosci 2011 (Body Weight...) : Collectively, our experiments reveal that high-fat diet induced, insulin dependent PI3K activation in VMH neurons contributes to obesity development
Arriola et al., J Biol Chem 2012 : We demonstrated that FOXO1 is expressed in murine gonadotrope cells and that insulin signaling increased FOXO1 phosphorylation and cytoplasmic localization in a PI3K dependent manner
Hirose et al., Metabolism 2001 (Insulin Resistance) : Denervation caused a decline in the insulin induced binding of p85 regulatory subunit of PI 3-K to IRS-1 to 61 % ( P < .001 ) and IRS-1 associated PI 3-K activity to 57 % ( P < .01 )
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
Andò et al., Mol Cell Endocrinol 2005 : Interestingly, in the presence of a disruptor of insulin signaling wortmannin, an inhibitor of PI3K , the intrinsic activity of G6PDH drops
O'Farrell et al., PLoS Biol 2013 : Both Stit and insulin receptor (InR) signaling activate PI3K-I and drive cellular proliferation and tissue growth
Ito et al., J Lipid Res 2011 (Obesity) : Furthermore, insulin increased both Akt and JNK phosphorylation, which was abrogated by the PI3K inhibitors
Schulman et al., Curr Hypertens Rep 2009 (Cardiovascular Diseases...) : In states of insulin resistance, insulin activation of PI3K is selectively impaired, whereas the MAPK pathway is spared and activated normally
Nadler et al., Am J Physiol Endocrinol Metab 2001 (Insulin Resistance) : Thus BtB6 mice demonstrate the dissociation of insulin stimulated PI3K activity and Akt/PKB activation and represent a useful model to investigate the causes of insulin resistance in humans
Cho et al., International journal of molecular sciences 2008 : This review focuses on the contribution of natural inhibitor or compound in our understanding of the mechanism by which insulin induces , especially in PI3K/PDK1/PKB signaling
Zawalich et al., J Endocrinol 2002 (Obesity) : They also suggest that, as insulin resistance develops in peripheral tissues, a potential result of impaired PI3K activation, the same biochemical anomaly in beta-cells promotes a linked increase in insulin secretion to maintain glucose homeostasis
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
Uehara et al., Eur J Biochem 1999 : We previously discovered that insulin activates Ras and that this is mediated by wortmannin-sensitive PI 3-K ... Interestingly, treating 3T3-L1 cells with PTX attenuates the activation by insulin of both the Ras-MAPK cascade and PI 3-K
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
Chaussade et al., Biochem J 2007 : Surprisingly, in J774.2 macrophage cells, insulin signalling to PKB was inhibited to a similar extent by inhibitors of p110alpha , p110beta or p110delta
Miura et al., Biochim Biophys Acta 1999 (Insulin Resistance) : We have examined the effect of TNF-alpha on insulin induced glucose uptake and activations of tyrosine kinase, IRS-1, PI3K and PKC in rat adipocytes
Lin et al., Biochem Biophys Res Commun 1998 (Carcinoma, Hepatocellular...) : Phosphatidylinositol 3-kinase is required for the regulation of hepatitis B surface antigen production and mitogen activated protein kinase activation by insulin but not by TPA
Choi et al., J Recept Signal Transduct Res 2004 : To study the role of PI3K in insulin stimulation of ERK, we employed PI3K inhibitor LY294002 and mouse embryonic R- fibroblasts lacking IGF-1 receptors ... In these R- cells, PI3K inhibition by LY294002 enhanced insulin stimulation of ERK phosphorylation whereas LY294002 inhibited insulin stimulation of Akt phosphorylation ... Increased insulin stimulation of ERK by PI3K inhibition was mediated by the MEK/ERK pathway, but did not involve inhibitory Ser259 phosphorylation of raf that was reported to be mediated by Akt ... In summary, PI3K inhibition in R- cells enhanced insulin stimulation of ERK phosphorylation by mechanisms involving enhancement of IRS-1 tyrosine phosphorylation, IRS-1-Grb2 complex formation and the ras/MEK/ERK pathway
Kralik et al., Endocrinology 2002 : Insulin , but not hyperosmolarity, clearly increased the activities of PI3K and Akt ... C2-ceramide did not alter insulin stimulated PI3K activity, but did decrease the ability of insulin to activate Akt and GLUT4 translocation
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
Choi et al., Korean J Intern Med 2010 (Diabetes Mellitus, Type 2...) : Although the mechanisms underlying insulin resistance are not completely understood in skeletal muscle, it is thought to result, at least in part, from impaired insulin dependent PI3K activation and downstream signaling
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
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
Sharma et al., Mol Cell Biol 1997 : Thus, interference with the IRS-1-IR interaction inhibits insulin stimulated IRS-1 and Shc phosphorylation, PI 3-K enzymatic activity, p70s6k activation, MAPK phosphorylation and cell cycle progression
Das et al., Mol Cell Endocrinol 2013 : PI3K inhibitors, wortmannin and LY294002 blocked insulin , but not 17a, 20ß-DHP induced GVBD
Fiory et al., J Biol Chem 2004 : PI3K inhibition also reduced insulin degradation and intact insulin release by 50 and 75 %, respectively
Lizcano et al., Biochem J 2003 : In mammalian cells, insulin induced PI3K ( phosphoinositide 3-kinase ) activation, generates the lipid second messenger PtdIns ( 3,4,5 ) P ( 3 ), which is thought to play a key role in triggering the activation of S6K
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
Okamoto et al., Biochem J 1993 : These results indicate that the specific activity of PI3K is increased by insulin stimulation without detectable tyrosine phosphorylation of PI3K itself in Fao cells ... The majority of the insulin activated portion of PI3K is associated with pTyr containing proteins including IRS-1, which suggests that this is important for activation of PI3K by insulin
Hawkins et al., J Biol Chem 1999 : To determine the time course of GlcN induced defects in insulin stimulated PI3K activity and peripheral insulin action, GlcN was administered for 30, 60, 90, or 120 min during 2-h euglycemic, hyperinsulinemic clamp studies ... Activation of muscle PI3K by insulin was attenuated following only 30 min of GlcN infusion ( GlcN 30 min = 1.5-fold versus saline = 2.5-fold stimulation ; p < 0.05 )
Tao et al., Journal of molecular signaling 2010 : Our results showed that 5-aminoimidazole-4-carboxamide-1 ribonucleoside ( AICAR ) greatly enhanced the ability of insulin to stimulate the insulin receptor substrate-1 (IRS1) associated PI3K activity in differentiated 3T3-F442a adipocytes, leading to increased Akt phosphorylation at S473, whereas insulin stimulated activation of mTOR was diminished
Chen et al., Pancreas 2005 (Diabetes Mellitus, Type 2) : The PI3K inhibitor wortmannin suppressed pV-induced insulin release at 3.3 mmol/L but not at 16.7 mmol/L glucose in both GK and Wistar rat islets
Fang et al., Mol Cell Biol 2002 : PI3K inhibitors block insulin- but not LPA induced GSK-3 phosphorylation
Staubs et al., J Biol Chem 1998 : 2 ) This PDGF induced phosphorylation of IRS-1 leads to a significant decrease in insulin stimulated PI3K activity
Trümper et al., Ann N Y Acad Sci 2000 : Insulin and IGF-1 stimulated PI 3-K activity was mainly associated with insulin receptor substrate (IRS) isoforms IRS-1 and IRS-2 and less so with the IRS-isoform Grb-2 associated binder-1 (Gab-1)
Chowdhury et al., Diabetologia 2013 : PI3K inhibition only slightly attenuated glucose stimulated insulin secretion from monolayers, but substantially reduced that from pseudoislets and human and mouse islets without suppressing the glucose induced [ Ca ( 2+ ) ] c response ... We propose that islet architecture is critical for proper beta cell mitochondrial metabolism and IRS-1 signalling, and that PI3K regulates insulin secretion at a step distal to the elevation of [ Ca ( 2+ ) ] c
Yu et al., Acta Biochim Biophys Sin (Shanghai) 2006 : Insulin also strongly activated both PI3K and the downstream effector Akt
Berger et al., Biochem Biophys Res Commun 1994 : Phosphatidylinositol 3-kinase ( PI 3-kinase ) is acutely stimulated by insulin but its role in regulating glucose metabolism is still not fully understood
Miele et al., J Biol Chem 2003 : In contrast, insulin dependent IRS-1 and IRS-2 tyrosine phosphorylation was severely reduced in cells preincubated with HGA for 24 h. Insulin stimulated association of PI3K with IRS-1 and IRS-2, and PI3K activity were reduced by HGA in parallel with the changes in IRS tyrosine phosphorylation, while Grb2-IRS association was unchanged
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
Desbois-Mouthon et al., Endocrinology 2000 : Insulin inhibition of JNKs was mediated by PI 3-K , as it was blocked by wortmannin and LY294002 and required the de novo synthesis of a phosphatase ( s ), as it was abolished by orthovanadate and actinomycin D. MKP-1 was a good candidate because 1 ) insulin stimulation of MKP-1 expression correlated with insulin inhibition of JNKs ; 2 ) insulin stimulation of MKP-1 expression, like insulin inhibition of JNKs, was mediated by PI 3-K ; and 3 ) the transient expression of an antisense MKP-1 RNA reduced the insulin inhibitory effect on JNKs
Lee et al., J Cell Physiol 2009 : Cell adhesion to BM promotes insulin stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and association of PI3K with IRS-1, whereas cells cultured on stromal ECM are inefficient in transducing these post-receptor events
Imai et al., Life Sci 2003 (Calcium Signaling) : SGK1 is one of the protein-serine/threonine kinases that is activated by insulin in a PI3K dependent manner
Wolff et al., Comb Chem High Throughput Screen 2006 : Upon stimulation of the hIR with insulin-like growth factor-1 (IGF-1) , PI3K was activated to phosphorylate phosphatidylinositol ( PtdIns ) -4,5-bisphosphate at the 3-position, resulting in the recruitment of AKT1-EGFP to the plasma membrane
Plastaras et al., Cancer Biol Ther 2008 (Gastrointestinal Neoplasms) : PI3K/Akt signaling is stimulated by insulin
Freychet et al., Bull Mem Acad R Med Belg 1996 (Disease Models, Animal...) : Insulin activation of PI3-K is markedly diminished in obese mice ; starving the obese animals restores normal responses of PI3-K, glucose transport, and glycogen synthesis, to insulin
Yasui et al., J Vasc Res 2008 : These data suggest that K ( ATP ) channel activation by insulin is mediated by PI3-K
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
Faraj et al., J Endocrinol 2006 (Diabetes Mellitus, Type 2...) : In healthy young men, adiponutrin expression is upregulated [ corrected ] by hyperinsulinemia and is related to basal and/or insulin stimulated p85alpha PI3K , HKII, adiponectin, and leptin expression levels
Del Turco et al., Curr Pharm Des 2013 (Cardiovascular Diseases...) : These mechanisms selectively impair PI3K dependent insulin in vascular endothelium harming endothelial balance and strengthening the evidence of the close association between metabolic and cardiovascular disease
Andreelli et al., Diabetologia 2000 (Diabetes Mellitus, Type 2) : Because we have shown in an earlier study that there is also a defective regulation of p85 alpha PI3K gene expression in response to insulin , these data support the hypothesis that alterations in the regulation of gene expression could be involved in the pathogenesis of Type II diabetes
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
Simoncini et al., Arterioscler Thromb Vasc Biol 2003 : Furthermore, we characterized the subsequent steps in the activation of the PI3K/Akt signaling cascade, comparing the molecular events that follow insulin or estradiol activation of PI3K
González et al., Int J Mol Med 2005 (Diabetes Mellitus, Type 2) : Apart from the much higher basal PI3K activity and impaired response to insulin of p44/42 MAP kinases in the diabetic patients, the changes in enzyme activity caused by either hormone or peptide, although not identical, were essentially comparable
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
Yan et al., Biochem J 2008 : The activation of the AGC ( protein kinase A/protein kinase G/protein kinase C ) -family kinase SGK1 ( serum- and glucocorticoid induced kinase 1 ) by insulin via PI3K ( phosphoinositide 3-kinase ) signalling has been appreciated for almost 10 years
Jiang et al., Frontiers in bioscience : a journal and virtual library 2002 (Diabetes Mellitus, Type 2) : In the current review, we will discuss the role of these molecules in insulin mediated activation of PI3K , the rational for targeting these molecules for diabetes treatment, and some critical issues in terms of drug development
Lee et al., Endocrinology 2008 : Protein kinase C-zeta, a downstream effector of phosphatidylinositol 3-kinase (PI3K), phosphorylates insulin receptor substrate (IRS)-1 on serine residues impairing activation of PI3K in response to insulin ... Significant insulin stimulated increases in PI3K activity was coimmunoprecipitated with all IRS isoforms ... In cells overexpressing PKC-zeta there was marked inhibition of insulin stimulated PI3K activity associated with IRS-1, -3 and -4 but not IRS-2
Lavie et al., J Neurochem 1996 (Neuroblastoma) : Preincubation with 1 mM carbachol inhibited the insulin stimulated PI3K activity in a time dependent manner, with half-maximal and maximal inhibition times of 4 and 15 min, respectively ... Addition of the cell-permeable homologue didecanoyl-CDP-DAG to intact cells inhibited insulin stimulated PI3K activity up to 75 %, with an IC50 of 0.5 microM, a result that further supports a proposed lipid mediated inhibition of PI3K
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
Hers et al., Biochem J 2005 : The effect of insulin on phosphorylation of both these sites required the activation of PI3K and the MAPKs ( mitogen activated protein kinases ) ERK1/2 ( extracellular-signal regulated kinase 1 and 2 ), but not the activation of mTOR ( mammalian target of rapamycin ) /p70S6 kinase, JNK ( c-Jun N-terminal kinase ) or p38MAPK
Ivins Zito et al., J Cell Physiol 2004 : 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
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
Miyake et al., J Clin Invest 2002 (Glucose Intolerance...) : Systemic infusion of an adenovirus encoding a dominant negative mutant of PI 3-K ( ( Delta ) p85 ) resulted in liver-specific expression of this protein and in inhibition of the insulin induced activation of PI 3-K in the liver within 3 days, without affecting insulin signaling in skeletal muscle ... The mice also exhibited marked decreases in the serum concentrations of FFAs and triglyceride and suppression of insulin induced PI 3-K activation in adipose tissue, probably due to the associated hyperinsulinemia
Phung et al., J Biol Chem 1997 : Current studies demonstrate that the PI 3-K inhibitor wortmannin inhibits both basal and insulin stimulated PI 3-K activities ... To link PI 3-K activation to insulin action on apoB, we investigated whether insulin induced localization of activated PI 3-K to the endoplasmic reticulum ( ER ), where apoB biogenesis is initiated ... Insulin stimulates a significant increase in PI 3-K activity associated with insulin receptor substrate-1 as well as an increase in insulin receptor substrate-1/PI 3-K mass in LDM ... Insulin stimulates PI 3-K activity in smooth and rough microsomes isolated from rat hepatocytes, the latter of which contain rough ER as demonstrated by electron microscopy ... Studies indicate that 1 ) PI 3-K activity is necessary for insulin dependent inhibition of apoB secretion by rat hepatocytes ; 2 ) insulin action leads to the activation and localization of PI 3-K in an ER fraction containing apoB ; and 3 ) insulin stimulates PI 3-K activity in the rough ER
Villarreal et al., Regul Pept 2010 : Role of IRS-4 in PI3-K activation by insulin in HepG2 cells, modulation by Angiotensin II ... We report also Ins induced PI3-K activation mediated by IRS-4
Carrillo et al., Endocrinology 2001 : From these findings it can be concluded that both PI 3-K and MAPK pathways, but not p70 S6-kinase, are involved in the short-term activation of PK-L by insulin in rat hepatocytes
Gulati et al., Biochem Soc Trans 2007 : Nutrient overload induces constitutive S6K1 ( S6 kinase 1 ) activation, which leads to insulin resistance by suppressing insulin induced class I PI3K ( phosphoinositide 3-kinase ) signalling [ Um, Frigerio, Watanabe, Picard, Joaquin, Sticker, Fumagalli, Allegrini, Kozma, Auwerx and Thomas ( 2004 ) Nature 431, 200-205 ]
Singh et al., Metabolism 2003 (Insulin Resistance) : In EXP-2, the high-fat diet reduced insulin stimulated glucose transport, in part, by impairing insulin stimulated PI3-K activation and glucose transporter translocation
Ma et al., Endocrinology 2004 (Acute Disease...) : In contrast, insulin induced tyrosine phosphorylation of IRS-1/2 and association between IRS-1/2 and PI3K were dramatically reduced after hemorrhage
Song et al., J Biol Chem 2013 (Diabetes Mellitus, Type 2...) : Increased insulin sensitivity was also confirmed after daily injection of emodin for 8 days using an insulin tolerance test and insulin stimulated PI3K phosphorylation in wild type and high fat diet induced diabetic mouse models
Furukawa et al., Cell Metab 2005 : Inactivation of ROK also reduces insulin stimulated IRS-1 tyrosine phosphorylation and PI3K activity
Maeno et al., J Biol Chem 2012 (Metabolic Diseases) : In this study, it was observed that PKC activation differentially inhibited insulin receptor substrate 1/2 ( IRS1/2 ) signaling of insulin 's activation of PI3K/eNOS by decreasing only tyrosine phosphorylation of IRS2
Borradaile et al., Diabetes 2003 (Carcinoma, Hepatocellular...) : Insulin and naringenin increased HepG2 cell PI3K activity and decreased insulin receptor substrate (IRS)-2 levels
Di Guglielmo et al., Mol Cell Biochem 1998 : Furthermore, studies with isolated rat adipocytes reveal the EN to be the principle site of insulin stimulated IRS-1 tyrosine phosphorylation and associated PI3K activation
Mohan et al., Science signaling 2013 (Cardiomegaly) : Activation of cardiac phosphoinositide 3-kinase a (PI3Ka) by growth factors, such as insulin , or activation of PI3K? downstream of heterotrimeric guanine nucleotide binding protein ( G protein ) -coupled receptors stimulates the activity of the kinase Akt, which phosphorylates and inhibits glycogen synthase kinase-3 ( GSK-3 )
Heydrick et al., J Clin Invest 1993 (Diabetes Mellitus, Type 2...) : Insulin did not affect total PI3K activity
Gliozzo et al., J Cell Biochem 1998 (Breast Neoplasms) : In MDA-MB157 and MCF-10A cells, insulin stimulated PI3-K activity three- to fourfold ... In ZR-75-1 cells, however, insulin did not stimulate PI3-K activity
Davidson et al., Am J Physiol Endocrinol Metab 2002 (Body Weight) : With brief time matched CR, reduced visceral fat mass precedes increased insulin sensitivity ; transient reduction in fructose 6-phosphate may trigger more persistent changes but does not coincide with enhanced insulin action ; and PI3K is essential for insulin stimulated 3-O-methylglucose transport in CR as well as AL rats, although insulin stimulated PI3K is not significantly greater in CR compared with AL animals
Liu et al., Eur J Cell Biol 2006 : These results indicate that PI3K plays different roles in the activation of Ras/ERK1/2 signaling by insulin and EGF, and that insulin stimulated, but not EGF stimulated, ERK1/2 and Akt signalings diverge at PI3K
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
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
Chandrasekher et al., Invest Ophthalmol Vis Sci 2000 : Phosphatidylinositol 3-kinase in bovine lens and its stimulation by insulin and IGF-1
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
Kingham et al., J Cell Sci 2009 : By comparison, pharmacological inhibition or siRNA mediated knockdown of p110alpha had no effect on mESC self-renewal per se, but instead appeared to reduce proliferation, which was accompanied by inhibition of leukaemia inhibitory factor (LIF) and insulin induced PI3K signalling
Wang et al., Diabetes 2013 : Insulin stimulated PI3K activity and phosphoinositide ( 3,4,5 ) -triphosphate production are enhanced by Paqr3 deletion and reduced by PAQR3 overexpression in hepatocytes
Di Santo et al., Journal of thrombosis and haemostasis : JTH 2011 (Thrombosis) : The results demonstrated that, in MN interacting with activated PLT : ( i ) TF activity, antigen and mRNA were low until 8-10 h and dramatically increased thereafter, up to 24 h ; ( ii ) according to the kinetics of TF expression in MN, GSK3ß undergoes phosphorylation on serine 9, a process associated with down-regulation of enzyme activity ; ( iii ) pharmacological blockade of GSK3 further increased TF expression and was accompanied by increased accumulation of NF-kB, in the nucleus ; ( iv ) blockade of phosphoinositide-3 kinase ( PI(3)K ) by wortmannin inhibited PLT induced TF expression ; and ( v ) according to the established role of the GSK3 downstream insulin receptor, insulin increased PLT induced TF expression in a PI(3)K dependent manner
Knight et al., Cell 2006 : A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling
Worrall et al., Mol Endocrinol 2002 : A negative role for Ca ( 2+ ) is also indicated in proximal insulin signaling steps, in that, depletion of intracellular Ca ( 2+ ) blocks IRS1 serine/threonine phosphorylation and enhances insulin stimulated protein-protein interaction and PI3K activity
Lee et al., Am J Physiol Endocrinol Metab 2012 (Diabetes Mellitus, Type 2...) : Insulin stimulated PI3K activity in skeletal muscle and adipose tissue of DIO mice was significantly reduced ~50-65 %, but this was restored completely by INT131 therapy
Rowland et al., Mol Cell Biol 2011 : Insulin increased 14-3-3 binding to RhoGAP22 fourfold, and this effect was PI3K dependent
Sajan et al., J Clin Endocrinol Metab 2004 (Obesity) : Relative to adipocytes of lean women, insulin stimulated [ ( 3 ) H ] 2-deoxyglucose uptake and activation of insulin receptor substrate-1/PI3K and aPKCs, but not PKB, were diminished in adipocytes of obese women
Kawabe et al., J Hypertens 2000 (Insulin Resistance) : Insulin stimulated activities of IRS-1 and PI3-K , but not MAPK activity, were also attenuated in the presence of high concentrations of glucose
Pandey et al., Endocrinology 2002 : Expression of a dominant negative mutant of Akt1 or class I PI3K inhibited the insulin stimulation of PI3K/Akt1 signaling without affecting phosphorylation of IkappaBalpha
Niswender et al., Diabetes 2003 (Anorexia...) : To test the hypothesis that hypothalamic insulin action involves intracellular PI3K signaling, we used histochemical and biochemical methods to determine the effect of insulin on hypothalamic IRS-PI3K activity
Terauchi et al., Nat Genet 1999 (Hypoglycemia) : Insulin stimulated PI3K activity associated with insulin receptor substrates (IRSs) was mediated via full-length p85 alpha in wild-type mice, but via the p50 alpha alternative splicing isoform of the same gene in Pik3r1-/- mice
Moissoglu et al., Biochem Biophys Res Commun 2005 (Cell Transformation, Neoplastic) : Interestingly, FAK was required for full activation of PI3K by PDGF whereas the activation of PI3K by insulin was significantly increased in FAK-/- cells
Huang et al., J Neurochem 2004 (Synaptic Transmission) : These results suggest that a PI3K/PKC dependent insulin signaling, which controls postsynaptic surface AMPA receptor numbers through PP-independent endocytosis, may be a major expression mechanism of insulin-LTD in hippocampal CA1 neurons
Lee et al., Experimental biology and medicine (Maywood, N.J.) 2003 : Additionally, the possible role for PI 3-K and PDE in leptin induced control of acetylcholine induced insulin secretion was examined
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
Martinez-deMena et al., J Mol Endocrinol 2005 : PI3K is stimulated by insulin and serum, and NE increases the effect of insulin
Xu et al., J Clin Invest 2005 (Synaptic Transmission) : We developed mice in which a fluorescent reporter for PI3K activity is targeted to either Agrp or POMC neurons and used 2-photon microscopy to measure dynamic regulation of PI3K by insulin and leptin in brain slices
Wong et al., Biochem Pharmacol 2011 (Glucose Intolerance...) : In corresponding Ang-IV treated animals, insulin induced IRAP and PI3K interaction, activation of pAkt and GLUT4 translocation, but no corresponding activation of IR, IRS-1 and IRS-1-PI3K coupling were observed
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