Hyperglycemia markedly enhances skeletal muscle glycogen synthase activity in diabetic, but not in normal conscious rats.
Both hyperinsulinemia and hyperglycemia stimulate skeletal muscle glucose uptake. However, the intracellular metabolic fate of the phosphorylated glucose may be different when the prevalent stimulus for glucose uptake is hyperinsulinemia or hyperglycemia. To define the impact of hyperglycemia on the intracellular glucose disposal, we studied control and diabetic conscious rats under four experimental conditions: 1) basal insulin and basal glucose; 2) basal insulin and high glucose; 3) high insulin and basal glucose; and 4) high insulin and high glucose. Under both basal insulin (130 pM) and high insulin (2500 pM), hyperglycemia (15 mM) increased glucose uptake and muscle and liver glycogen synthesis similarly in control and diabetic rats. Hyperglycemia resulted in a more significant decline in the muscle G-6-P concentration in diabetic rats than in control rats, suggesting activation of intracellular glucose metabolism. The diabetic skeletal muscle glycogen synthase was severely resistant to insulin stimulation compared with control (FV0.1 = 0.31 +/- 0.04 vs. 0.49 +/- 0.03; Km = 0.19 +/- 0.05 vs. 0.10 +/- 0.01 mM; P < 0.01), but it was markedly responsive to glucose stimulation under both basal (FV0.1 = 0.38 +/- 0.03 vs. 0.21 +/- 0.03; Km = 0.10 +/- 0.01 vs. 0.35 +/- 0.08 mM) and high insulin (FV0.1 = 0.65 +/- 0.07 vs. 0.31 +/- 0.04; Km = 0.11 +/- 0.02 vs. 0.19 +/- 0.05 mM). By contrast, in control rats, hyperglycemia did not exert any stimulatory effect on skeletal muscle glycogen synthase. Thus, some metabolic alteration associated with the diabetic state renders the skeletal muscle glycogen synthase selectively responsive to glucose stimulation. This may represent a compensatory mechanism for the severe impairment in insulin's activation of this enzyme in diabetes.
Farrace
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S
Department of Medicine, University of Texas Health Science Center, San Antonio.
Rossetti
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L
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism*; D006019:Glycolysis; D006943:Hyperglycemia / Q000097:blood / Q000201:enzymology* / Q000378:metabolism; D007700:Kinetics; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000201:enzymology*; D010180:Pancreatectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D001786:Blood Glucose; D008112:Liver Glycogen; D006003:Glycogen; D006006:Glycogen Synthase; D005947:Glucose