Effect of Chronic Hyperglycemia on Glucose Metabolism in Subjects With Normal Glucose Tolerance

Diabetes
Chris ShannonR A DeFronzo

Abstract

Chronic hyperglycemia causes insulin resistance, but the inheritability of glucotoxicity and the underlying mechanisms are unclear. We examined the effect of 3 days of hyperglycemia on glucose disposal, enzyme activities, insulin signaling, and protein O-GlcNAcylation in skeletal muscle of individuals without (FH-) or with (FH+) family history of type 2 diabetes. Twenty-five subjects with normal glucose tolerance received a [3-3H]glucose euglycemic insulin clamp, indirect calorimetry, and vastus-lateralis biopsies before and after 3 days of saline (n = 5) or glucose (n = 10 FH- and 10 FH+) infusion to raise plasma glucose by ∼45 mg/dL. At baseline, FH+ had lower insulin-stimulated glucose oxidation and total glucose disposal (TGD) but similar nonoxidative glucose disposal and basal endogenous glucose production (bEGP) compared with FH- After 3 days of glucose infusion, bEGP and glucose oxidation were markedly increased, whereas nonoxidative glucose disposal and TGD were lower versus baseline, with no differences between FH- and FH+ subjects. Hyperglycemia doubled skeletal muscle glycogen content and impaired activation of glycogen synthase (GS), pyruvate dehydrogenase, and Akt, but protein O-GlcNAcylation was unchanged. Insulin...Continue Reading

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Citations

May 16, 2020·International Journal of Endocrinology·Marta Letizia HribalGiorgio Sesti
Jun 19, 2021·Organic & Biomolecular Chemistry·Ishfaq Ahmad Rather, Rashid Ali

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Methods Mentioned

BETA
biopsies
biopsy

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