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Research Article Free access | 10.1172/JCI114462

Insulin resistance is associated with reduced fasting and insulin-stimulated glycogen synthase phosphatase activity in human skeletal muscle.

Y Kida, A Esposito-Del Puente, C Bogardus, and D M Mott

Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016.

Find articles by Kida, Y. in: PubMed | Google Scholar

Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016.

Find articles by Esposito-Del Puente, A. in: PubMed | Google Scholar

Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016.

Find articles by Bogardus, C. in: PubMed | Google Scholar

Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016.

Find articles by Mott, D. in: PubMed | Google Scholar

Published February 1, 1990 - More info

Published in Volume 85, Issue 2 on February 1, 1990
J Clin Invest. 1990;85(2):476–481. https://doi.org/10.1172/JCI114462.
© 1990 The American Society for Clinical Investigation
Published February 1, 1990 - Version history
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Abstract

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.

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