Reactive Oxygen Species Enhance Insulin Sensitivity

被引：472

作者：

Loh, Kim ^{[1
]}

Deng, Haiyang ^{[1
]}

Fukushima, Atsushi ^{[1
]}

Cai, Xiaochu ^{[1
]}

Boivin, Benoit ^{[3
]}

Galic, Sandra ^{[1
]}

Bruce, Clinton

Shields, Benjamin J. ^{[1
]}

Skiba, Beata

Ooms, Lisa M. ^{[1
]}

Stepto, Nigel ^{[2
]}

Wu, Ben ^{[1
]}

Mitchell, Christina A. ^{[1
]}

Tonks, Nicholas K. ^{[3
]}

Watt, Matthew J. ^{[2
]}

Febbraio, Mark A.

Crack, Peter J. ^{[4
]}

Andrikopoulos, Sofianos ^{[5
]}

Tiganis, Tony ^{[1
]}

机构：

[1] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia

[2] Monash Univ, Dept Physiol, Clayton, Vic 3800, Australia

[3] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[4] Univ Melbourne, Dept Pharmacol, Melbourne, Vic 3010, Australia

[5] Univ Melbourne, Dept Med, Heidelberg Repatriat Hosp, Heidelberg, Vic 3081, Australia

来源：

CELL METABOLISM | 2009年 / 10卷 / 04期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

PROTEIN-TYROSINE PHOSPHATASES; CELLULAR GLUTATHIONE-PEROXIDASE; TUMOR-SUPPRESSOR PTEN; SKELETAL-MUSCLE; REVERSIBLE OXIDATION; HYDROGEN-PEROXIDE; SIGNAL-TRANSDUCTION; GLUCOSE-TRANSPORT; RESISTANCE; MICE;

D O I：

10.1016/j.cmet.2009.08.009

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Chronic reactive oxygen species (ROS) production by mitochondria may contribute to the development of insulin resistance, a primary feature of type 2 diabetes. In recent years it has become apparent that ROS generation in response to physiological stimuli such as insulin may also facilitate signaling by reversibly oxidizing and inhibiting protein tyrosine phosphatases (PTPs). Here we report that mice lacking one of the key enzymes involved in the elimination of physiological ROS, glutathione peroxidase 1 (Gpx1), were protected from high-fat-diet-induced insulin resistance. The increased insulin sensitivity in Gpx1(-/-) mice was attributed to insulin-induced phosphatidylinositol-3-kinase/Akt signaling and glucose uptake in muscle and could be reversed by the antioxidant N-acetylcysteine. Increased insulin signaling correlated with enhanced oxidation of the PTP family member PTEN, which terminates signals generated by phosphatidylinositol-3-kinase. These studies provide causal evidence for the enhancement of insulin signaling by ROS in vivo.

引用

页码：260 / 272

页数：13

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