Insulin receptor function and glycogen synthase activity in skeletal muscle biopsies from patients with insulin-dependent diabetes mellitus: effects of physical training

The Journal of Clinical Endocrinology and Metabolism
J F BakO Pedersen

Abstract

This study was designed to examine the mechanisms causing peripheral insulin resistance in patients with insulin-dependent diabetes mellitus (IDDM) by studying insulin receptor function and glycogen synthase activity in biopsies of skeletal muscle. The results in seven such patients were compared with values obtained in a group of sedentary, age- and sex-matched normal subjects. In addition, since physical training appears to improve insulin sensitivity, the IDDM patients were reexamined after physical training for 6 weeks. The mean maximal glycogen synthase activity was lower in the diabetic than in the normal group [34.5 +/- 10.6 (+/- SD) vs. 45.7 +/- 8.6 nmol/mg protein.min; P less than 0.05], whereas there was no difference in the half-maximal activation constant (A0.5) for glucose-6-phosphate. Likewise, the mean yield of wheat germ agglutinin-purified insulin receptors recovered per mg muscle was 21% lower in the muscle biopsies from the diabetic patients (47 +/- 8 vs. 66 +/- 20 fmol/100 mg; P less than 0.05. However, basal and insulin-stimulated receptor kinase activities, expressed as phosphorylation of the synthetic peptide poly-Glu-Tyr(4:1), were identical in the two groups. After physical training in the diabetic pati...Continue Reading

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