Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes.

Article Details

Citation

Nikoulina SE, Ciaraldi TP, Mudaliar S, Mohideen P, Carter L, Henry RR

Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes.

Diabetes. 2000 Feb;49(2):263-71.

PubMed ID
10868943 [ View in PubMed
]
Abstract

Glycogen synthase (GS) activity is reduced in skeletal muscle of type 2 diabetes, despite normal protein expression, consistent with altered GS regulation. Glycogen synthase kinase-3 (GSK-3) is involved in regulation (phosphorylation and deactivation) of GS. To access the potential role of GSK-3 in insulin resistance and reduced GS activity in type 2 diabetes, the expression and activity of GSK-3 were studied in biopsies of vastus lateralis from type 2 and nondiabetic subjects before and after 3-h hyperinsulinemic (300 mU x m(-2) x min(-1))-euglycemic clamps. The specific activity of GSK-3alpha did not differ between nondiabetic and diabetic muscle and was decreased similarly after 3-h insulin infusion. However, protein levels of both alpha and beta isoforms of GSK-3 were elevated (approximately 30%) in diabetic muscle compared with lean (P < 0.01) and weight-matched obese nondiabetic subjects (P < 0.05) and were unchanged by insulin infusion. Thus, both basal and insulin-stimulated total GSK-3 activities were elevated by approximately twofold in diabetic muscle. GSK-3 expression was related to in vivo insulin action, as GSK-3 protein was negatively correlated with maximal insulin-stimulated glucose disposal rates. In summary, GSK-3 protein levels and total activities are 1) elevated in type 2 diabetic muscle independent of obesity and 2) inversely correlated with both GS activity and maximally insulin-stimulated glucose disposal. We conclude that increased GSK-3 expression in diabetic muscle may contribute to the impaired GS activity and skeletal muscle insulin resistance present in type 2 diabetes.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Glycogen synthase kinase-3 betaP49841Details
Glycogen synthase kinase-3 alphaP49840Details