Metformin suppresses glucose-6-phosphatase expression by a complex I inhibition and AMPK activation-independent mechanism

被引：82

作者：

Ota, Shinichi ^{[1
]}

Horigome, Kazuhiko ^{[1
]}

Ishii, Takayuki ^{[1
]}

Nakai, Michio ^{[1
]}

Hayashi, Koji ^{[1
]}

Kawamura, Takao ^{[1
]}

Kishino, Akiyoshi ^{[1
]}

Taiji, Mutsuo ^{[1
]}

Kimura, Toru ^{[1
]}

机构：

[1] Dainippon Sumitomo Pharma Co Ltd, Osaka 5540022, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 388卷 / 02期

关键词：

Metformin; Glucose-6-phosphatase; AMPK; Complex I; NDI1; Diabetes; PROTEIN-KINASE; RESPIRATORY-CHAIN; ADENOVIRUS; LIVER; GLUCONEOGENESIS; ADIPOCYTES; GENOME; CELLS;

D O I：

10.1016/j.bbrc.2009.07.164

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Metformin is widely used as a hypoglycemic agent for the treatment of type 2 diabetes. Both metformin and rotenone, an inhibitor of respiratory chain complex I, suppressed glucose-6-phosphatase (G6pc), a rate limiting enzyme of liver glucose production, mRNA expression in a rat hepatoma cell line accompanied by a reduction of intracellular ATP concentration and an activation of AMP-activated protein kinase (AMPK). When yeast NADH-quinone oxidoreductase 1 (NDI1) gene was introduced into the cells, neither inhibition of ATP synthesis nor activation of AMPK was induced by these agents. Interestingly, in contrast to rotenone treatment, G6pc mRNA down-regulation was observed in the NDI1 expressing cells after metformin treatment. Since NDI1 can functionally complement the complex I under the presence of metformin or rotenone, our results indicate that metformin induces down-regulation of G6pc expression through an inhibition of complex I and an activation of AMPK-independent mechanism. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：311 / 316

页数：6