An energetic tale of AMPK-independent effects of metformin

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 recentl...

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Published in:The Journal of clinical investigation Vol. 120; no. 7; pp. 2267 - 2270
Main Authors: Miller, Russell A., Birnbaum, Morris J.
Format: Journal Article
Language:English
Published: United States American Society for Clinical Investigation 01.07.2010
Subjects:
AMP-Activated Protein Kinases
Biomedical research
Carbohydrate Metabolism
Care and treatment
Cyclic adenylic acid
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
Gene expression
Gene Expression - drug effects
Genetic aspects
Health aspects
Hepatocytes - drug effects
Hepatocytes - metabolism
Humans
Hypoglycemic Agents - metabolism
Hypoglycemic Agents - pharmacology
Hypoglycemic Agents - therapeutic use
Insulin Resistance
Liver - drug effects
Liver - metabolism
Metformin
Metformin - metabolism
Metformin - pharmacology
Metformin - therapeutic use
Physiological aspects
Protein kinases
Protein Kinases - metabolism
Protein Kinases - pharmacology
Signal Transduction - drug effects
Type 2 diabetes
United States
ISSN:0021-9738, 1558-8238, 1558-8238
Online Access:Get full text
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Summary: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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ISSN:0021-9738
1558-8238
1558-8238
DOI:10.1172/JCI43661