Metformin induces PGC-1a expression and selectively affects hepatic PGC-1a functions

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F14%3A10282278" target="_blank" >RIV/00216208:11160/14:10282278 - isvavai.cz</a>
Result on the web
<a href="http://onlinelibrary.wiley.com/doi/10.1111/bph.12585/full" target="_blank" >http://onlinelibrary.wiley.com/doi/10.1111/bph.12585/full</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/bph.12585" target="_blank" >10.1111/bph.12585</a>

Result language
angličtina
Original language name
Metformin induces PGC-1a expression and selectively affects hepatic PGC-1a functions
Original language description
Background and Purpose The objective of this study was to determine how the AMPK activating antidiabetic drug metformin affects the major activator of hepatic gluconeogenesis, PPAR coactivator 1 (PGC-1) and liver functions regulated by PGC-1. Experimental Approach Mouse and human primary hepatocytes and mice in vivo were treated with metformin. Adenoviral overexpression, siRNA and reporter gene constructs were used for mechanistic studies. Key Results Metformin increased PGC-1 mRNA and protein expression in mouse primary hepatocytes. 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) (another AMPK activator) had the opposite effect. Metformin also increased PGC-1 in human primary hepatocytes; this effect of metformin was abolished by AMPK inhibitorcompound C and sirtuin 1 siRNA. AMPK overexpression by AMPK-Ad also increased PGC-1. Whereas metformin increased PGC-1, it down-regulated gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Fu
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FR - Pharmacology and apothecary chemistry
OECD FORD branch
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Project
<a href="/en/project/GAP303%2F12%2F0472" target="_blank" >GAP303/12/0472: Novel mechanisms of CYP3A4 enzyme regulation based on posttranslational modification of nuclear receptors - implications for pharmacotherapy</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2014
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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