Insulin-dependent H2O2 production is higher in muscle fibers of mice fed with a high-fat diet

Alejandra Espinosa, Cristian Campos, Alexis Díaz-Vegas, José E. Galgani, Nevenka Juretic, César Osorio-Fuentealba, José L. Bucarey, Gladys Tapia, Rodrigo Valenzuela, Ariel Contreras-Ferrat, Paola Llanos, Enrique Jaimovich

Resultado de la investigación: Contribución a una revistaArtículo

24 Citas (Scopus)

Resumen

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.

Idioma originalInglés
Páginas (desde-hasta)15740-15754
Número de páginas15
PublicaciónInternational Journal of Molecular Sciences
Volumen14
N.º8
DOI
EstadoPublicada - 12 ago 2013

Áreas temáticas de ASJC Scopus

  • Catálisis
  • Biología molecular
  • Espectroscopia
  • Informática aplicada
  • Química física y teórica
  • Química orgánica
  • Química inorgánica

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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. (2013). Insulin-dependent H2O2 production is higher in muscle fibers of mice fed with a high-fat diet. International Journal of Molecular Sciences, 14(8), 15740-15754. https://doi.org/10.3390/ijms140815740