Alejandra Espinosa 1,2, * , Cristian Campos 1 , Alexis Díaz-Vegas 1,2 , José E. Galgani 3 , Nevenka

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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
Alejandra Espinosa 1,2, * , Cristian Campos 1 , Alexis Díaz-Vegas 1,2 , José E. Galgani 3 , Nevenka Juretic smd 4 , César Osorio-Fuentealba 2 , José L. Bucarey 5 , Gladys Tapia 4 , Rodrigo Valenzuela 4 , Ariel Contreras-Ferrat 2 , Paola Llanos 2  and Enrique Jaimovich 2,4
1 School smd of Medical Technology, Faculty of Medicine, University of Chile, Santiago 8380455, Chile 2 Center smd for Molecular Studies of the Cell, Santiago 8380453, Chile 3 Nutrition smd Department, Faculty of Medicine, University of Chile, Santiago 8380453, Chile 4 Faculty of Medicine, Institute of Biomedical Sciences, Santiago 8380453, Chile 5 School of Medicine, University of Valparaíso, Valparaíso 2341369, Chile
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 (H 2 O 2 ) produced by NADPH oxidase 2 (NOX2) is involved in signaling pathways triggered by insulin. smd We evaluated oxidative status in skeletal muscle fibers from insulin-resistant and control mice by determining H 2 O 2 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 H 2 O 2 release and decreased reduced-to-oxidized glutathione ratio (GSH/GSSG). In addition, p47 phox and gp91 phox (NOX2 subunits) mRNA levels were also high (~3-fold in HFD mice compared to controls), smd 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 smd glucose smd uptake restored. Our results indicate that insulin-resistant mice have increased H 2 O 2 release upon insulin stimulation when compared with control animals, which appears smd to be mediated by an increase in NOX2 expression.
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 H 2 O 2 Production Is Higher in Muscle Fibers of Mice Fed with a High-Fat Diet. Int. J. Mol. Sci. 2013 , 14 , 15740-15754. AMA Style
Espinosa smd 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 smd H 2 O 2 Production Is Higher in Muscle Fibers of Mice Fed with a High-Fat Diet. International smd Journal smd of Molecular Sciences . 2013; 14(8):15740-15754. Chicago/Turabian Style
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 H 2 O 2 Production Is Higher in Muscle Fibers of Mice Fed with a High-Fat Diet." Int. J. Mol. Sci. 14, no. 8: 15740-15754.
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