Regulation of Glucose Production in the Pathogenesis of Type 2 Diabetes

Current Diabetes Reports
Ashot Sargsyan, Mark A Herman

Abstract

Increased glucose production associated with hepatic insulin resistance contributes to the development of hyperglycemia in T2D. The molecular mechanisms accounting for increased glucose production remain controversial. Our aims were to review recent literature concerning molecular mechanisms regulating glucose production and to discuss these mechanisms in the context of physiological experiments and observations in humans and large animal models. Genetic intervention studies in rodents demonstrate that insulin can control hepatic glucose production through both direct effects on the liver, and through indirect effects to inhibit adipose tissue lipolysis and limit gluconeogenic substrate delivery. However, recent experiments in canine models indicate that the direct effects of insulin on the liver are dominant over the indirect effects to regulate glucose production. Recent molecular studies have also identified insulin-independent mechanisms by which hepatocytes sense intrahepatic carbohydrate levels to regulate carbohydrate disposal. Dysregulation of hepatic carbohydrate sensing systems may participate in increased glucose production in the development of diabetes.

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Citations

Jul 31, 2020·The Journal of Biological Chemistry·Subhashis BanerjeeAndrew A Butler
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Cheng Li, Zhenxia Hu
Dec 19, 2020·Journal of Drug Targeting·Faezeh Almasi, Fatemeh Mohammadipanah
Apr 5, 2021·The Journal of Biological Chemistry·Liora S KatzMark A Herman

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