Defective insulin response of cyclic adenosine monophosphate-dependent protein kinase in insulin-resistant humans.

Y Kida; B L Nyomba; C Bogardus; D M Mott

doi:10.1172/JCI115045

Defective insulin response of cyclic adenosine monophosphate-dependent protein kinase in insulin-resistant humans.

Y Kida, B L Nyomba, C Bogardus, and D M Mott

Published February 1, 1991 - More info

View PDF

Abstract

Insulin-stimulated glycogen synthase activity in human muscle correlates with insulin-mediated glucose disposal and is reduced in insulin-resistant subjects. Inhibition of the cyclic AMP-dependent protein kinase (A-kinase) is considered as a possible mechanism of insulin action for glycogen synthase activation. In this study, we investigated the time course of insulin action on human muscle A-kinase activity during a 2-h insulin infusion in 13 insulin-sensitive (group S) and 7 insulin-resistant subjects (group R). Muscle biopsies were obtained from quadriceps femoris muscle at times 0, 10, 20, 40, and 120 min. Insulin infusion resulted in significant inhibition of A-kinase activity at 20 and/or 40 min using 0.2, 0.6, and 1.0 microM cyclic AMP in group S. A-kinase activities both before and after insulin administration were lower in group S than in group R using 0.6 microM cyclic AMP. The decrease in apparent affinity for cyclic AMP during insulin infusion was larger for group S compared with group R. Glycogen synthase activity increased significantly after insulin infusion in both groups and was higher in group S compared with group R. The data suggest that a defective response of A-kinase to insulin in insulin-resistant subjects could contribute to their reduced insulin stimulation of skeletal muscle glycogen synthase.