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
Aug 15, 2008·The Journal of Biological Chemistry·Meenalakshmi M MariappanBalakuntalam S Kasinath
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
Nov 24, 1999·The Journal of Biological Chemistry·M Roques, H Vidal
Apr 19, 2000·The Journal of Clinical Endocrinology and Metabolism·X HuangL Groop
Feb 28, 2004·Diabetes·Michael GasterHenning Beck-Nielsen
Dec 15, 2018·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Michael Gaster
Jul 9, 2004·The Journal of Clinical Endocrinology and Metabolism·E A McIntyreM Walker
Sep 11, 2001·The Journal of Clinical Endocrinology and Metabolism·S E NikoulinaR R Henry
Mar 28, 2002·Diabetes·Michael GasterHenning Beck-Nielsen
Feb 18, 2005·Diabetes, Obesity & Metabolism·Lars Hansen, Oluf Pedersen
Feb 7, 2004·European Journal of Clinical Investigation·J FredrikssonM Orho-Melander
Jun 28, 2002·Diabetes·Svetlana E NikoulinaRobert R Henry
Dec 4, 2001·Biochimica Et Biophysica Acta·M GasterH Beck-Nielsen
Jul 11, 2003·Journal of Medicinal Chemistry·Preben H OlesenBo F Hansen
Dec 2, 2008·Biochimica Et Biophysica Acta·Sara FröjdöLuciano Pirola