Glutathione peroxidase 3 mediates the antioxidant effect of peroxisome proliferator-activated receptor gamma in human skeletal muscle cells

Cited 126 time in Web of Science Cited 131 time in Scopus

Chung, Sung Soo; Kim, Min; Youn, Byoung-Soo; Lee, Nam Seok; Park, Ji Woo; Lee, In Kyu; Lee, Yun Sok; Kim, Jae Bum; Cho, Young Min; Lee, Hong Kyu; Park, Kyong Soo

Issue Date
American Society for Microbiology
Mol Cell Biol. 29(1):20-30
AnimalsAntioxidants/*metabolismBiological Transport/drug effectsDiabetes Mellitus/enzymologyDisease Models, AnimalExtracellular Space/drug effects/metabolismGlucose/metabolismGlutathione Peroxidase/*metabolismHumansHydrogen Peroxide/metabolismInsulin/metabolismIntracellular Space/drug effects/metabolismMiceMice, Inbred C57BLMuscle Cells/drug effects/*enzymologyMuscle, Skeletal/*cytology/*enzymologyPPAR gamma/*metabolismResponse ElementsSignal Transduction/drug effectsThiazolidinediones/pharmacology
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 (PPARgamma) 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 PPARgamma 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 PPARgamma-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 PPARgamma is exclusively mediated by GPx3 and further imply that GPx3 may be a therapeutic target for insulin resistance and diabetes mellitus.
1098-5549 (Electronic)
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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