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

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 b...

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Published in:International journal of molecular sciences 2013-07, Vol.14 (8), p.15740-15754
Main Authors: 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
Format: Article
Language:English
Subjects:
Animals
apocynin
Diabetes
Diet, High-Fat
Electronic mail systems
Glucose
Glutathione - metabolism
Homeostasis
Hydrogen Peroxide - metabolism
Insulin - metabolism
Insulin Resistance
Kinases
Male
Medicine
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Mice
Mice, Inbred C57BL
Muscle Fibers, Skeletal - metabolism
Musculoskeletal system
NADPH Oxidase 2
NADPH Oxidases - genetics
NADPH Oxidases - metabolism
NOX2
Obesity
Oxidation-Reduction
Pathophysiology
Phosphorylation
Physiology
Proteins
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms140815740