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01-09-2019 | Insulins | Pathogenesis of Type 2 Diabetes and Insulin Resistance (M-E Patti, Section Editor)

Regulation of Glucose Production in the Pathogenesis of Type 2 Diabetes

Published in: Current Diabetes Reports | Issue 9/2019

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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Title: Regulation of Glucose Production in the Pathogenesis of Type 2 Diabetes
Publication date: 01-09-2019
Keywords: Insulins
Insulins
Published in: Current Diabetes Reports / Issue 9/2019
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI: https://doi.org/10.1007/s11892-019-1195-5

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STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

At a glance: The STEP trials

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