title: Reactive oxygen species enhance insulin sensitivity.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
authors.forename: Kim
authors.initials: K
authors.lastname: Loh
authors.forename: Haiyang
authors.initials: H
authors.lastname: Deng
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukushima
authors.forename: Xiaochu
authors.initials: X
authors.lastname: Cai
authors.forename: Benoit
authors.initials: B
authors.lastname: Boivin
authors.forename: Sandra
authors.initials: S
authors.lastname: Galic
authors.forename: Clinton
authors.initials: C
authors.lastname: Bruce
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Shields
authors.forename: Beata
authors.initials: B
authors.lastname: Skiba
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Ooms
authors.forename: Nigel
authors.initials: N
authors.lastname: Stepto
authors.forename: Ben
authors.initials: B
authors.lastname: Wu
authors.forename: Christina A
authors.initials: CA
authors.lastname: Mitchell
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Tonks
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Watt
authors.forename: Mark A
authors.initials: MA
authors.lastname: Febbraio
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Crack
authors.forename: Sofianos
authors.initials: S
authors.lastname: Andrikopoulos
authors.forename: Tony
authors.initials: T
authors.lastname: Tiganis
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002478:Cells, Cultured; D004734:Energy Metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009765:Obesity / Q000378:metabolism; D010084:Oxidation-Reduction; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D007328:Insulin; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D000111:Acetylcysteine; D000094765:Glutathione Peroxidase GPX1