An Energetic Tale of AMPK-independent Effects of Metformin

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2010 Jun 26

PMID 20577046

Citations 71

Authors

Russell A Miller

Morris J Birnbaum

Affiliations

Soon will be listed here.

Abstract

Metformin has become a mainstay in the modest therapeutic armamentarium for the treatment of the insulin resistance of type 2 diabetes mellitus. Although metformin functions primarily by reducing hepatic glucose output, the molecular mechanism mediating this effect had remained elusive until recently. Metformin impairs ATP production, activating the conserved sensor of nutritional stress AMP-activated protein kinase (AMPK), thus providing a plausible and generally accepted model for suppression of gluconeogenic gene expression and glucose output. In this issue of the JCI, Foretz et al. refute this hypothesis by showing that AMPK is dispensable for the effects of metformin on hepatic glucose output in primary hepatocytes; rather, their data suggest that the antidiabetic effects of metformin in the liver are mediated directly by reducing energy charge.

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