Effect of glucose phosphorylation on the activation by insulin of skeletal muscle glycogen synthase.
The effect of insulin injection on skeletal muscle glycogen synthase activation was studied in anesthetized, normal, fed rats. Insulin stimulated the conversion of glycogen synthase to the active I form, increased the concentration of glucose 6-phosphate, and activated glycogen synthase phosphatase. A close correlation between glucose 6-phosphate concentrations, per cent glycogen synthase in the active I form, and phosphatase activity was found. When boiled extracts of muscle from control and insulin-injected animals were added to glycogen pellets containing phosphatase 1G, the difference in phosphatase activity between muscle extracts from insulin-injected and control rats was restored, indicating that the phosphatase was activated by heat-stable factors. Deproteinized muscle extracts from control and insulin-injected rats, at concentrations equivalent to those present in muscle, were tested for the activation of glycogen synthase by purified protein phosphatases 1 and 2A. The activation with the insulin extracts was four-fold larger than with the control extracts. When the extracts from insulin-injected rats were treated with glucose 6-phosphatase, the difference in activation with the control rat extracts was canceled. It would appear that, as in other insulin sensitive tissues, in skeletal muscle the increase in glucose 6-phosphate subsequent to the activation of glucose transport by insulin contributes to the activation of glycogen synthase.
Villar-Palasi
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Department of Pharmacology, Medical School, University of Virginia, Charlottesville 22908, USA.
D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D005958:Glucosephosphates / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D006007:Glycogen-Synthase-D Phosphatase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009132:Muscles / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D005958:Glucosephosphates; D007328:Insulin; D006006:Glycogen Synthase; D006007:Glycogen-Synthase-D Phosphatase