Abstract: Insulin resistance is defined as a reduced ability of insulin to stimulate glucose utilization. C57BL/6 mice fed with a high-fat diet (HFD) are a model of insulin resistance. In skeletal muscle, hydrogen peroxide (H2O2) produced by NADPH oxidase 2 (NOX2) is involved in signaling pathways triggered by insulin. We evaluated oxidative status in skeletal muscle fibers from insulin-resistant and control mice by determining H2O2 generation (HyPer probe), reduced-to-oxidized glutathione ratio and NOX2 expression. After eight weeks of HFD, insulin-dependent glucose uptake was impaired in skeletal muscle fibers when compared with control muscle fibers. Insulin-resistant mice showed increased insulin-stimulated H2O2 release and decreased reduced-to-oxidized glutathione ratio (GSH/GSSG). In addition, p47phox and gp91phox (NOX2 subunits) mRNA levels were also high (~3-fold in HFD mice compared to controls), while protein levels were 6.8- and 1.6-fold higher, respectively. Using apocynin (NOX2 inhibitor) during the HFD feeding period, the oxidative intracellular environment was diminished and skeletal muscle insulin-dependent glucose uptake restored. Our results indicate that insulin-resistant mice have increased H2O2 release upon insulin stimulation when compared with control animals, which appears to be mediated by an increase in NOX2 expression.
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Espinosa, A.; Campos, C.; Díaz-Vegas, A.; Galgani, J.E.; Juretic, N.; Osorio-Fuentealba, C.; Bucarey, J.L.; Tapia, G.; Valenzuela, R.; Contreras-Ferrat, A.; Llanos, P.; Jaimovich, E. Insulin-Dependent H2O2 Production Is Higher in Muscle Fibers of Mice Fed with a High-Fat Diet. Int. J. Mol. Sci. 2013, 14, 15740-15754.
Espinosa A, Campos C, Díaz-Vegas A, Galgani JE, Juretic N, Osorio-Fuentealba C, Bucarey JL, Tapia G, Valenzuela R, Contreras-Ferrat A, Llanos P, Jaimovich E. Insulin-Dependent H2O2 Production Is Higher in Muscle Fibers of Mice Fed with a High-Fat Diet. International Journal of Molecular Sciences. 2013; 14(8):15740-15754.
Espinosa, Alejandra; Campos, Cristian; Díaz-Vegas, Alexis; Galgani, José E.; Juretic, Nevenka; Osorio-Fuentealba, César; Bucarey, José L.; Tapia, Gladys; Valenzuela, Rodrigo; Contreras-Ferrat, Ariel; Llanos, Paola; Jaimovich, Enrique. 2013. "Insulin-Dependent H2O2 Production Is Higher in Muscle Fibers of Mice Fed with a High-Fat Diet." Int. J. Mol. Sci. 14, no. 8: 15740-15754.