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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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

Název v anglickém jazyce

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

Popis výsledku anglicky

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

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

—

Projekt

<a href="/cs/project/GAP303%2F12%2F0472" target="_blank" >GAP303/12/0472: Studium mechanizmů regulace biotransformačního enzymu CYP3A4 prostřednictvím posttranslačních modifikací nukleárních receptorů-význam pro terapii</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

British Journal of Pharmacology

ISSN

0007-1188

e-ISSN

—

Svazek periodika

171

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

2351-2363

Kód UT WoS článku

000334156100008

EID výsledku v databázi Scopus

—