Insulin-mediated glycogen synthase activity in muscle of spontaneously insulin-resistant and diabetic rhesus monkeys.
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.
Ortmeyer
H K
HK
Department of Physiology, School of Medicine, University of Maryland at Baltimore 21201.
Bodkin
N L
NL
Hansen
B C
BC
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology*; D005215:Fasting; D005947:Glucose / Q000378:metabolism / Q000502:physiology; D006006:Glycogen Synthase / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism / Q000502:physiology*; D007333:Insulin Resistance; D008253:Macaca mulatta; D009132:Muscles / Q000201:enzymology*; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D006006:Glycogen Synthase; D005947:Glucose