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- Title
Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes.
- Authors
Nikoulina, Svetlana E.; Ciaraldi, Theodore P.; Mudaliar, Sunder; Mohideen, Pharis; Carter, Leslie; Henry, Robert R.; Nikoulina, S E; Ciaraldi, T P; Mudaliar, S; Mohideen, P; Carter, L; Henry, R R
- 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.
- Subjects
TYPE 2 diabetes; BLOOD sugar; GLYCOGEN synthesis; METABOLISM; COMPARATIVE studies; INSULIN; INSULIN resistance; ISOENZYMES; RESEARCH methodology; MEDICAL cooperation; PHOSPHORYLATION; PHOSPHOTRANSFERASES; REFERENCE values; RESEARCH; TRANSFERASES; EVALUATION research; SKELETAL muscle
- Publication
Diabetes, 2000, Vol 49, Issue 2, p263
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.49.2.263