Postabsorptive respiratory quotient and insulin-stimulated glucose storage rate in nondiabetic pima indians are related To glycogen synthase fractional activity in cultured myoblasts.
A decreased ratio of fat to carbohydrate oxidation rate (an elevated respiratory quotient) predicts the development of obesity. Skeletal muscle accounts for a major fraction of total body lipid oxidation and is the principle site for reduced glucose storage in insulin-resistant subjects. The potentially important role that muscle has in promoting obesity or insulin resistance may be based on metabolic control intrinsic to skeletal muscle. Cultured skeletal muscle provides a system to examine the importance of inherent metabolic traits in muscle biopsies from obese and insulin-resistant subjects. Glycogen synthase fractional activity (GSFA) was measured in cultured myoblasts from 21 Pima Indians characterized in vivo using indirect calorimetry and a euglycemic hyperinsulinemic clamp. Basal GSFA in cultured muscle cells is inversely correlated with postabsorptive respiratory quotient of the muscle donors (r = -0.66, P = 0.001) and with in vivo high dose insulin-stimulated glucose storage rates (r = 0.47, P = 0.04). These results indicate that the postabsorptive respiratory quotients and insulin-mediated glucose storage rates in vivo share a common regulatory mechanism with GSFA in cultured myoblasts. Abnormal regulation of glycogen synthase phosphorylation state may be an intrinsic defect in skeletal muscle associated with obesity and insulin resistance.
Mott
D M
DM
Clinical Diabetes & Nutrition Section, National Institutes of Health, Phoenix, Arizona 85016, USA. dmott@phx.niddk.nih.gov
Pratley
R E
RE
Bogardus
C
C
D000328:Adult; D002151:Calorimetry; D050260:Carbohydrate Metabolism; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000235:genetics*; D005223:Fats / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology; D007198:Indians, North American; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology; D010766:Phosphorylation
D005223:Fats; D007328:Insulin; D006006:Glycogen Synthase; D005947:Glucose