INCREASED CONCENTRATIONS OF GLYCOGEN-SYNTHASE PROTEIN IN SKELETAL-MUSCLE OF PATIENTS WITH NIDDM

To examine whether changes in the glycogen synthase protein concentrat ion contribute to impaired insulin-stimulated glycogen metabolism in p atients with noninsulin-dependent diabetes mellitus (NIDDM), muscle bi opsies were taken before and after a 4-h euglycemic hyperinsulinemic c lamp to measure glycogen synthase activity and glycogen synthase prote in concentrations in 14 patients with NIDDM and in 17 control subjects . Nonoxidative glucose metabolism was reduced by 64% in patients with NIDDM compared with control subjects and correlated with insulin-stimu lated glycogen synthase activity (r = 0.55, P < 0.05). The concentrati on of glycogen synthase protein in skeletal muscle was higher in patie nts with NIDDM than in control subjects (6.75 +/- 0.88 vs. 4.41 +/- 0. 50 counts . min(-1).mu g protein(-1), P < 0.05), whereas there was no significant difference in glycogen synthase mRNA concentration between the two groups. The glycogen synthase protein concentration correlate d inversely with the rate of nonoxidative glucose metabolism (r = -0.6 3, P < 0.05). These findings indicate that the amount of glycogen synt hase protein is increased in skeletal muscle of patients with NIDDM. T he increase in the glycogen synthase protein may serve to compensate f or a functional defect in the activation of the enzyme by insulin.