Metformin stimulates FGF21 expression in primary hepatocytes
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Metformin stimulates FGF21 expression in primary hepatocytes. / Nygaard, Eva B; Vienberg, Sara G; Ørskov, Cathrine; Hansen, Harald S.; Andersen, Birgitte.
In: Experimental Diabetes Research, Vol. 2012, 2012, p. 465282.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Metformin stimulates FGF21 expression in primary hepatocytes
AU - Nygaard, Eva B
AU - Vienberg, Sara G
AU - Ørskov, Cathrine
AU - Hansen, Harald S.
AU - Andersen, Birgitte
N1 - Article ID 465282
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - AMP-Activated Protein Kinases
KW - Animals
KW - Cells, Cultured
KW - Enzyme Activation
KW - Fibroblast Growth Factors
KW - Hepatocytes
KW - Humans
KW - Hypoglycemic Agents
KW - Liver Glycogen
KW - Male
KW - Metformin
KW - Phosphorylation
KW - Protein Kinase Inhibitors
KW - Protein Processing, Post-Translational
KW - Protein Subunits
KW - Pyrazoles
KW - Pyrimidines
KW - RNA, Messenger
KW - Rats
KW - Rats, Sprague-Dawley
KW - Up-Regulation
U2 - 10.1155/2012/465282
DO - 10.1155/2012/465282
M3 - Journal article
C2 - 23118742
VL - 2012
SP - 465282
JO - Journal of Diabetes Research
JF - Journal of Diabetes Research
SN - 2314-6745
ER -
ID: 44796842