Gene interactions and pathways from curated databases and text-mining
J Endocrinol 2000, PMID: 11018758

Decreased Akt kinase activity and insulin resistance in C57BL/KsJ-Leprdb/db mice.

Shao, J; Yamashita, H; Qiao, L; Friedman, J E

Recent studies suggest that the serine/threonine kinase protein kinase B (PKB or Akt) is involved in the pathway for insulin-stimulated glucose transporter 4 (GLUT4) translocation and glucose uptake. In this study we examined the components of the Akt signaling pathway in skeletal muscle and adipose tissue in vivo from C57BL/KsJ-Lepr(db/db) mice (db/db), a model of obesity, insulin resistance, and type II diabetes. There were no changes in the protein levels of GLUT4, p85alpha, or Akt in tissues from db/db mice compared with non-diabetic littermate controls (+/+). In response to acute insulin administration, GLUT4 recruitment to the plasma membrane increased twofold in muscle and adipose tissue from +/+ mice, but was significantly reduced by 42-43% (P<0.05) in both tissues from db/db mice. Insulin increased Akt-Ser(473) phosphorylation by two- to fivefold in muscle and adipose tissue from all mice. However, in db/db mice, maximal Akt-Ser(473) phosphorylation was decreased by 32% (P<0.05) and 69% (P<0.05) in muscle and adipose tissue respectively. This decreased phosphorylation in db/db mice corresponded with a significant decrease in maximal Akt kinase activity using a glycogen synthase kinase-3 fusion protein as a substrate (P<0.05). The level of insulin-stimulated tyrosine phosphorylation of p85alpha from phosphatidylinositol 3 (PI 3)-kinase, which is upstream of Akt, was also reduced in muscle and adipose tissue from db/db mice (P<0.05); however, there was no change in extracellular signal-regulated kinase-1 or -2 phosphorylation. 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. However, impaired insulin signal transduction appears to be specific for the PI 3-kinase pathway of insulin signaling, while the MAP kinase pathway remained intact.

Diseases/Pathways annotated by Medline MESH: Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Insulin Resistance, Obesity
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Text Mining Data

glucose transporter 4 (GLUT4) → insulin: " Recent studies suggest that the serine/threonine kinase protein kinase B ( PKB or Akt ) is involved in the pathway for insulin stimulated glucose transporter 4 (GLUT4) translocation and glucose uptake "

Akt-Ser → Insulin: " Insulin increased Akt-Ser ( 473 ) phosphorylation by two- to fivefold in muscle and adipose tissue from all mice "

p85alpha → insulin: " The level of insulin stimulated tyrosine phosphorylation of p85alpha from phosphatidylinositol 3 (PI 3)-kinase, which is upstream of Akt, was also reduced in muscle and adipose tissue from db/db mice ( P < 0.05 ) ; however, there was no change in extracellular signal regulated kinase-1 or -2 phosphorylation "

Akt → insulin: " 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 "

Manually curated Databases

No curated data.