Glycogen synthase in diabetic rat skeletal muscle: activation by insulin.
Glycogen synthase in skeletal muscle of 3-day alloxan-diabetic rats was found to be in a less active state than in normal muscle. Both the activity ratio (activity without G6P divided by activity with 7.2 mM G6P at 4.4 mM UDPG, pH 7.8) and fractional velocity (activity with 0.25 mM G6P divided by activity with 10 mM G6P at 0.03 mM UDPG, pH 6.9) were significantly lower in the diabetic tissue. Correspondingly, the S0.5 for UDPG and A0.5 for G6P were significantly higher in diabetic tissue, suggesting decreased affinity for substrate and activator, respectively. The kinetic  changes in the diabetic synthase were identical whether the alloxan-treated animals were maintained on insulin for 7 days prior to withdrawal for 3 days, or studied 3 days immediately after alloxan treatment. The diabetes-induced changes in synthase could be reversed by injecting the diabetic rat with insulin 10 min prior to sacrifice. After insulin treatment, the S0.5 for UDPG and A0.5 for G6P decreased to control levels or lower and the activity ratios and fractional velocities increased to control levels or higher. The activity of glycogen synthase phosphatase was not decreased in diabetic skeletal muscle. This observation, coupled with the rapid response of the diabetic synthase to in vivo insulin treatment, suggests that, unlike the phosphatase in cardiac muscle and liver, the glycogen synthase phosphatase in skeletal muscle is not altered by the diabetic state.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D005958:Glucosephosphates / Q000494:pharmacology; D006006:Glycogen Synthase / Q000378:metabolism*; D006007:Glycogen-Synthase-D Phosphatase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D009132:Muscles / Q000201:enzymology; D051381:Rats; D014532:Uridine Diphosphate Glucose / Q000494:pharmacology
D005958:Glucosephosphates; D007328:Insulin; D006006:Glycogen Synthase; D006007:Glycogen-Synthase-D Phosphatase; D014532:Uridine Diphosphate Glucose