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Int. J. Mol. Sci. 2013, 14(8), 15740-15754; doi:10.3390/ijms140815740
Article

Insulin-Dependent H2O2 Production Is Higher in Muscle Fibers of Mice Fed with a High-Fat Diet

1,2,* , 1
, 1,2
, 3
, 4
, 2
, 5
, 4
, 4
, 2
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 and 2,4
1 School of Medical Technology, Faculty of Medicine, University of Chile, Santiago 8380455, Chile 2 Center for Molecular Studies of the Cell, Santiago 8380453, Chile 3 Nutrition 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
* Author to whom correspondence should be addressed.
Received: 1 June 2013 / Revised: 20 July 2013 / Accepted: 24 July 2013 / Published: 29 July 2013
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
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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.
Keywords: obesity; NOX2; insulin resistance; apocynin obesity; NOX2; insulin resistance; apocynin
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

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