AJP - Regulatory, Integrative and Comparative Physiology, Vol 265, Issue 3 552-R558, Copyright © 1993 by American Physiological Society
Insulin-mediated glycogen synthase activity in muscle of spontaneously insulin-resistant and diabetic rhesus monkeys
H. K. Ortmeyer, N. L. Bodkin and B. C. Hansen
Department of Physiology, School of Medicine, University of Maryland at Baltimore 21201.
Altered insulin action on glycogen synthase activity has been well
recognized in non-insulin-dependent diabetes, and some prior evidence has
suggested this alteration may be one of the earliest disturbances preceding
the development of diabetes. The present study, using the spontaneously
insulin-resistant and diabetic rhesus monkey, examined insulin's effect on
glycogen synthase at the earliest point of identification of developing
diabetes. The normal monkeys (n = 11) had a greater insulin-mediated change
in glycogen synthase-independent activity compared with the
hyperinsulinemic (n = 8) (P < 0.05) and diabetic (n = 8) (P < 0.01)
monkeys. Compared with normal monkeys, the diabetic monkeys had lower basal
and insulin-stimulated total glycogen synthase activity (P < 0.05).
Monkeys with normal beta-cell responsiveness to intravenous glucose had
greater insulin-mediated change in glycogen synthase fractional velocity
compared with those with exaggerated (P < 0.01) or absent beta-cell
responses to glucose (P < 0.05). We conclude that an alteration in
insulin action on glycogen synthase is present as early as beta-cell
hyperresponsiveness, one of the earliest detected abnormalities in the
progression toward diabetes.
