Regulation of glycogen synthase activity in cultured skeletal muscle cells from subjects with type II diabetes: role of chronic hyperinsulinemia and hyperglycemia

Diabetes
S E NikoulinaR R Henry

Abstract

Human skeletal muscle cultures (HSMCs) from type II diabetic subjects were used to determine whether metabolic abnormalities such as hyperglycemia or hyperinsulinemia contribute to the defective muscle glycogen synthase (GS) activity present in this disorder. Following approximately 6 weeks of growth, diabetic cultures were fused for 4 days in normal, hyperglycemia, or hyperinsulinemia medium. Fusion of diabetic HSMCs in hyperglycemia medium (20 mmol/l vs. 5.5 mmol/l) had no effect on GS fractional velocity (FV) or mRNA levels, but impaired acute insulin-stimulation of glycogen synthesis and GS activity at 0.1 mmol/l glucose-6-phosphate, and reduced GS protein content by approximately 15% (P < 0.05). Fusion of diabetic muscle cultures in hyperinsulinemia medium (30 micromol/l vs. 22 pmol/l) improved basal GS activity, increasing the reduced GS FV by approximately 50% (P < 0.05), and decreasing the elevated Km(0.1) (half-maximal substrate concentration) by approximately 47% (P < 0.05). Hyperinsulinemia also significantly increased (P < 0.05) the reduced GS mRNA and protein levels of diabetic muscle to levels similar to that in nondiabetic subjects. In contrast to the improvements in the basal state, hyperinsulinemia completely a...Continue Reading

Citations

Apr 7, 2000·Molecular Aspects of Medicine·J MercierR Ventura
Mar 2, 2002·Journal of Diabetes and Its Complications·T P CiaraldiR R Henry
Jul 18, 2002·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·A Pérez-MartinJ Mercier
Sep 11, 2008·Expert Opinion on Therapeutic Targets·Katrina MacAulay, James R Woodgett
Mar 11, 2003·The Journal of Pharmacology and Experimental Therapeutics·Batya PlotkinHagit Eldar-Finkelman
Dec 15, 2018·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Michael Gaster
Sep 11, 2001·The Journal of Clinical Endocrinology and Metabolism·S E NikoulinaR R Henry
Feb 18, 2005·Diabetes, Obesity & Metabolism·Lars Hansen, Oluf Pedersen
Feb 7, 2004·European Journal of Clinical Investigation·J FredrikssonM Orho-Melander
Dec 2, 2008·Biochimica Et Biophysica Acta·Sara FröjdöLuciano Pirola

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