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Regulation of Glucose Production in the Pathogenesis of Type 2 Diabetes

  • Pathogenesis of Type 2 Diabetes and Insulin Resistance (M-E Patti, Section Editor)
  • Published:
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Abstract

Purpose of Review

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.

Recent Findings

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.

Summary

Dysregulation of hepatic carbohydrate sensing systems may participate in increased glucose production in the development of diabetes.

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Funding

This work was supported by NIH R01DK100425 (M.A.H.) and American Diabetes Association 1-19-PDF-088 (A.S.).

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  1. Duke Molecular Physiology Institute, Duke University, Durham, NC, USA

    Ashot Sargsyan & Mark A. Herman

  2. Division of Diabetes, Endocrinology, and Metabolism, Duke University, Durham, NC, USA

    Mark A. Herman

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  1. Ashot Sargsyan
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Correspondence to Mark A. Herman.

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Ashot Sargsyan declares that he has no conflict of interest.

Mark A. Herman reports personal fees from Alkermes Pharmaceuticals and grants from Eli Lilly and Co.

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Sargsyan, A., Herman, M.A. Regulation of Glucose Production in the Pathogenesis of Type 2 Diabetes. Curr Diab Rep 19, 77 (2019). https://doi.org/10.1007/s11892-019-1195-5

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