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Updated: Jun 19, 2026

Production and Detection of Reactive Oxygen Species (ROS) in Cancers
Published on: November 21, 2011
Reactive oxygen species enhance insulin sensitivity
Kim Loh1, Haiyang Deng, Atsushi Fukushima
1Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
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.
Insights
Mice lacking glutathione peroxidase 1 (Gpx1) showed improved insulin sensitivity and were protected from diet-induced insulin resistance. This suggests reactive oxygen species (ROS) enhance insulin signaling in vivo.
Area of Science:
- Biochemistry
- Cellular Biology
- Metabolic Diseases
Background:
- Mitochondrial reactive oxygen species (ROS) production is implicated in insulin resistance and type 2 diabetes.
- Physiological ROS may modulate cell signaling by oxidizing protein tyrosine phosphatases (PTPs).
Purpose of the Study:
- To investigate the role of glutathione peroxidase 1 (Gpx1) in diet-induced insulin resistance.
- To determine if ROS signaling enhances insulin sensitivity in vivo.
Main Methods:
- Utilized Gpx1 knockout (Gpx1(-/-)) mice fed a high-fat diet.
- Assessed insulin sensitivity, glucose uptake, and PTP oxidation.
- Administered the antioxidant N-acetylcysteine.
Main Results:
- Gpx1(-/-) mice were protected from high-fat-diet-induced insulin resistance.
- Insulin sensitivity in Gpx1(-/-) mice was linked to enhanced phosphatidylinositol-3-kinase/Akt signaling and muscle glucose uptake.
- Antioxidant treatment reversed the increased insulin sensitivity.
- Observed enhanced oxidation of PTEN, a PTP that negatively regulates PI3K signaling.
Conclusions:
- These findings provide causal evidence that ROS enhance insulin signaling in vivo.
- Targeting ROS elimination pathways may offer therapeutic strategies for insulin resistance.
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