IMR Press / FBL / Volume 14 / Issue 3 / DOI: 10.2741/3301

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Current strategies for the inhibition of hepatic glucose production in type 2 diabetes
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1 Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville TN, 37232-0615, USA
Academic Editors:Catherine Kargar, Frederic De Ceuninck, Frederic De Ceuninck
Front. Biosci. (Landmark Ed) 2009, 14(3), 1169–1181; https://doi.org/10.2741/3301
Published: 1 January 2009
(This article belongs to the Special Issue New therapeutic approaches for type 2 diabetes)
Abstract

Diabetes is a complex disease involving multiple organs with dysregulation in glucose and lipid metabolism. Hepatic insulin insensitivity can contribute to elevated fasting glucose levels and impaired glucose tolerance in individuals with diabetes. Several currently available therapeutics address defects at the liver. Metformin inhibits glucose production, potentially through effects on AMPK. Thiazolidinediones activate PPAR-gamma and improve hepatic insulin sensitivity, primarily through indirect effects on lipid metabolism. Insulin analogs and secretagogues suppress glucose production and increase liver glucose utilization by both direct and indirect hepatic actions. Incretins, incretin mimetics, and dipeptidyl peptidase-4 inhibitors reduce postprandial hepatic glucose production by increasing insulin secretion and limiting glucagon release, as well as through possible direct effects on the liver. Pramlintide reduces the increase in plasma glucagon that occurs following a meal in individuals with diabetes, and may thereby suppress inappropriate stimulation of liver glucose production. Many other hepatic targets are being considered which may lead to alternative strategies for the treatment of diabetes. This review focuses on currently available therapeutics which target insulin resistance in the liver.

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