Impaired skeletal muscle glycogen synthase activation by insulin in the Goto-Kakizaki (G/K) rat.
The Goto-Kakizaki (G/K) rat is an animal model of non-insulin-dependent diabetes mellitus, with early hyperglycaemia, hyperinsulinaemia, and insulin resistance. We have studied the effect of insulin on the activation of glycogen synthase in the G/K rat and in the original parent strain, the Wistar rat. After insulin injection, glycogen synthase I activity, glycogen synthase phosphatase activity and glucose 6-phosphate content in skeletal muscle were significantly increased in the Wistar rats. In the G/K rats, insulin injection resulted in a reduced activation of skeletal muscle glycogen synthase, which was not significant when compared with the control rats without insulin, and no increases in glycogen synthase phosphatase and glucose 6-phosphate were seen. In adipose tissue the activation of glycogen synthase by insulin was normal in the G/K rats. Previous investigations have shown that glucose disappearance rates are low in the G/K rat. However, stimulation of glucose transport was reported to be normal in the G/K rat. A defective activation of glucose accumulation into glycogen by skeletal muscle may contribute to explain the hyperglycaemia in the G/K rat.
Villar-Palasi
C
C
Department of Pharmacology, University of Virginia School of Medicine Charlottesville.
Farese
R V
RV
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D004789:Enzyme Activation; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism*; D006007:Glycogen-Synthase-D Phosphatase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar
D005958:Glucosephosphates; D007328:Insulin; D019298:Glucose-6-Phosphate; D006006:Glycogen Synthase; D006007:Glycogen-Synthase-D Phosphatase