Insulin resistance is associated with reduced fasting and insulin-stimulated glycogen synthase phosphatase activity in human skeletal muscle.
Insulin-stimulated glycogen synthase activity in human skeletal muscle correlates with insulin-mediated glucose disposal rate (M) and is reduced in insulin-resistant subjects. We have previously reported reduced insulin-stimulated glycogen synthase activity associated with reduced fasting glycogen synthase phosphatase activity in skeletal muscle of insulin-resistant Pima Indians. In this study we investigated the time course for insulin stimulation of glycogen synthase and synthase phosphatase during a 2-h high-dose insulin infusion (600 mU/min per m2) in six insulin-sensitive caucasians (group S) and in five insulin-resistant Pima Indians (group R). Percutaneous muscle biopsies were obtained from the quadriceps femoris muscle after insulin infusion for 0, 10, 20, 40, and 120 min. In group S, insulin-stimulated glycogen synthase activity increased with time and was significantly higher than in group R. In group S, synthase phosphatase activity increased significantly by 25% at 10 min and then decreased gradually. No significant change in synthase phosphatase was seen in group R and activity was lower than group S at 0 to 20 min. These data suggest that a low basal synthase phosphatase activity and a defect in its response to insulin explain, at least in part, reduced insulin stimulation of skeletal muscle glycogen synthase associated with insulin resistance.
Kida
Y
Y
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016.
Esposito-Del Puente
A
A
Bogardus
C
C
Mott
D M
DM
D000255:Adenosine Triphosphate / Q000032:analysis; D000328:Adult; D004789:Enzyme Activation; D005215:Fasting; D005260:Female; D005947:Glucose / Q000378:metabolism; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000032:analysis; D006006:Glycogen Synthase / Q000032:analysis; D006007:Glycogen-Synthase-D Phosphatase / Q000032:analysis*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D009132:Muscles / Q000201:enzymology*; D010749:Phosphoprotein Phosphatases / Q000032:analysis*; D010766:Phosphorylation
D005958:Glucosephosphates; D007328:Insulin; D019298:Glucose-6-Phosphate; D000255:Adenosine Triphosphate; D006006:Glycogen Synthase; D010749:Phosphoprotein Phosphatases; D006007:Glycogen-Synthase-D Phosphatase; D005947:Glucose