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. 6.35 ± 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.
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Original Articles|
November 01 1992
Hyperglycemia Markedly Enhances Skeletal Muscle Glycogen Synthase Activity in Diabetic, But Not in Normal Conscious Rats
Stefano Farrace;
Stefano Farrace
Department of Medicine, University of Texas Health Science Center
San Antonio, Texas
Department of Medicine, Albert Einstein College of Medicine
Bronx, New York
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Luciano Rossetti
Luciano Rossetti
Department of Medicine, University of Texas Health Science Center
San Antonio, Texas
Department of Medicine, Albert Einstein College of Medicine
Bronx, New York
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Address correspondence and reprint requests to Luciano Rossetti, MD, Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461.
Diabetes 1992;41(11):1453–1463
Article history
Received:
February 28 1992
Revision Received:
May 07 1992
Accepted:
May 07 1992
PubMed:
1397721
Citation
Stefano Farrace, Luciano Rossetti; Hyperglycemia Markedly Enhances Skeletal Muscle Glycogen Synthase Activity in Diabetic, But Not in Normal Conscious Rats. Diabetes 1 November 1992; 41 (11): 1453–1463. https://doi.org/10.2337/diab.41.11.1453
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