S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Glutathione Peroxidase 3 Mediates the Antioxidant Effect of Peroxisome Proliferator-Activated Receptor gamma in Human Skeletal Muscle Cells
- Chung, Sung Soo; Kim, Min; Youn, Byoung-Soo; Lee, Nam Seok; Lee, In Kyu; Kim, Jae Bum; Lee, Hong Kyu; Park, Kyong Soo; Cho, Young Min; Lee, Yun Sok; Park, Ji Woo
- Issue Date
- AMER SOC MICROBIOLOGY
- MOLECULAR AND CELLULAR BIOLOGY; Vol.29 1; 20-30
- Oxidative stress plays an important role in the pathogenesis of insulin resistance and type 2 diabetes mellitus and in diabetic vascular complications. Thiazolidinediones (TZDs), a class of peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists, improve insulin sensitivity and are currently used for the treatment of type 2 diabetes mellitus. Here, we show that TZD prevents oxidative stress-induced insulin resistance in human skeletal muscle cells, as indicated by the increase in insulin-stimulated glucose uptake and insulin signaling. Importantly, TZD-mediated activation of PPAR gamma induces gene expression of glutathione peroxidase 3 (GPx3), which reduces extracellular H(2)O(2) levels causing insulin resistance in skeletal muscle cells. Inhibition of GPx3 expression prevents the antioxidant effects of TZDs on insulin action in oxidative stress-induced insulin-resistant cells, suggesting that GPx3 is required for the regulation of PPAR gamma-mediated antioxidant effects. Furthermore, reduced plasma GPx3 levels were found in patients with type 2 diabetes mellitus and in db/db/DIO mice. Collectively, these results suggest that the antioxidant effect of PPAR gamma is exclusively mediated by GPx3 and further imply that GPx3 may be a therapeutic target for insulin resistance and diabetes mellitus.
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