Metformin stimulates FGF21 expression in primary hepatocytes

Eva B Nygaard; Sara G Vienberg; Cathrine Ørskov; Harald S. Hansen; Birgitte Andersen

doi:10.1155/2012/465282

Metformin stimulates FGF21 expression in primary hepatocytes

Authors:

Nygaard, Eva B ;
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Section for Metabolic Receptology, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet
Vienberg, Sara G ;
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Section for Integrative Physiology, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet
Ørskov, Cathrine ;
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Section of Endocrinology Research, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
Hansen, Harald S. ;
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0000-0001-7360-7418
Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, Københavns Universitet
Andersen, Birgitte
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Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet

DOI:

10.1155/2012/465282

Abstract:

Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator of glucose and lipid metabolism; however, the exact mechanism of action and regulation of FGF21 is not fully understood. Metabolic status plays an important role in the regulation of FGF21, and we therefore examined whether metformin, an indirect AMPK-activator, regulates FGF21 expression in hepatocytes. FGF21 mRNA and protein expression were determined after incubation of primary cultured rat and human hepatocytes with metformin for 24 hours. To study the role of AMPK in the putative regulation of FGF21, hepatocytes were incubated with Compound C (an AMPK inhibitor) in the presence of metformin. A strong dose-dependent increase in FGF21 expression was observed in both rat and human hepatocytes treated with metformin. This effect was blocked by addition of the AMPK-inhibitor Compound C. The study shows that metformin is a potent inducer of hepatic FGF21 expression and that the effect of metformin seems to be mediated through AMPK activation. As FGF21 therapy normalizes blood glucose in animal models of type 2 diabetes, the induction of hepatic FGF21 by metformin might play an important role in metformin's antidiabetic effect.

Type:

Journal article

Language:

English

Published in:

Experimental Diabetes Research, 2012, Vol 2012

Keywords:

AMP-Activated Protein Kinases; Animals; Cells, Cultured; Enzyme Activation; Fibroblast Growth Factors; Hepatocytes; Humans; Hypoglycemic Agents; Liver Glycogen; Male; Metformin; Phosphorylation; Protein Kinase Inhibitors; Protein Processing, Post-Translational; Protein Subunits; Pyrazoles; Pyrimidines; RNA, Messenger; Rats; Rats, Sprague-Dawley; Up-Regulation

Main Research Area:

Medical science

Publication Status:

Published

Review type:

Peer Review

Submission year:

2012

Scientific Level:

Scientific

ID:

232292879

Metformin stimulates FGF21 expression in primary hepatocytes

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