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• W2023754969 abstract "The condition of oxidative stress arises when oxidant production exceeds antioxidant activity in cells and plasma. The overabundance of oxidants is mechanistically connected to the multifactorial etiology of insulin resistance, primarily in skeletal muscle tissue, and the subsequent development of type 2 diabetes. Two important mechanisms for this oxidant excess are (1) the mitochondrial overproduction of hydrogen peroxide and superoxide ion under conditions of energy surplus and (2) the enhanced activation of cellular NADPH oxidase via angiotensin II receptors. Several recent studies are reviewed that support the concept that direct exposure of mammalian skeletal muscle to an oxidant stress (including hydrogen peroxide) results in stimulation of the serine kinase p38 mitogen-activated protein kinase (p38 MAPK), and that the engagement of this stress-activated p38 MAPK signaling is mechanistically associated with diminished insulin-dependent stimulation of insulin signaling elements and glucose transport activity. The beneficial interactions between the antioxidant α-lipoic acid and the advanced glycation end-product inhibitor pyridoxamine that ameliorate oxidant stress-associated defects in whole-body and skeletal-muscle insulin action in the obese Zucker rat, a model of prediabetes, are also addressed. Overall, this review highlights the importance of oxidative stress in the development of insulin resistance in mammalian skeletal muscle tissue, at least in part via a p38-MAPK-dependent mechanism, and indicates that interventions that reduce this oxidative stress and oxidative damage can improve insulin action in insulin-resistant animal models. Strategies to prevent and ameliorate oxidative stress remain important in the overall treatment of insulin resistance and type 2 diabetes." @default.
• W2023754969 created "2016-06-24" @default.
• W2023754969 creator A5028358308 @default.
• W2023754969 creator A5032880718 @default.
• W2023754969 creator A5034834995 @default.
• W2023754969 date "2011-09-01" @default.
• W2023754969 modified "2023-10-14" @default.
• W2023754969 title "Oxidative stress and the etiology of insulin resistance and type 2 diabetes" @default.
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• W2023754969 doi "https://doi.org/10.1016/j.freeradbiomed.2010.12.005" @default.
• W2023754969 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3071882" @default.
• W2023754969 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21163347" @default.

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