title: Insulin-dependent H2O2 production is higher in muscle fibers of mice fed with a high-fat diet.
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.
authors.affiliation: School of Medical Technology, Faculty of Medicine, University of Chile, Santiago 8380455, Chile. bespinosa@med.uchile.cl
authors.forename: Alejandra
authors.initials: A
authors.lastname: Espinosa
authors.forename: Cristian
authors.initials: C
authors.lastname: Campos
authors.forename: Alexis
authors.initials: A
authors.lastname: Díaz-Vegas
authors.forename: José E
authors.initials: JE
authors.lastname: Galgani
authors.forename: Nevenka
authors.initials: N
authors.lastname: Juretic
authors.forename: César
authors.initials: C
authors.lastname: Osorio-Fuentealba
authors.forename: José L
authors.initials: JL
authors.lastname: Bucarey
authors.forename: Gladys
authors.initials: G
authors.lastname: Tapia
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Valenzuela
authors.forename: Ariel
authors.initials: A
authors.lastname: Contreras-Ferrat
authors.forename: Paola
authors.initials: P
authors.lastname: Llanos
authors.forename: Enrique
authors.initials: E
authors.lastname: Jaimovich
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D007328:Insulin; D008562:Membrane Glycoproteins; D006861:Hydrogen Peroxide; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D005978:Glutathione
references.citation: Physiol Rev. 2009 Jan;89(1):27-71
references.pmid: 19126754
references.citation: J Biol Chem. 2009 Jan 23;284(4):2568-75
references.pmid: 19028699
references.citation: J Biomed Biotechnol. 2010;2010:476279
references.pmid: 20445742
references.citation: Am J Cardiol. 2002 Sep 5;90(5A):11G-18G
references.pmid: 12231074
references.citation: Diabetes. 2005 Apr;54(4):959-67
references.pmid: 15793233
references.citation: Circulation. 2007 Feb 6;115(5):627-37
references.pmid: 17242275
references.citation: Physiol Rev. 2007 Jan;87(1):245-313
references.pmid: 17237347
references.citation: J Biol Chem. 2008 Sep 12;283(37):25567-25575
references.pmid: 18635540
references.citation: Food Funct. 2012 Dec;3(12):1319-23
references.pmid: 23007174
references.citation: J Cell Physiol. 2011 Apr;226(4):1110-7
references.pmid: 20857410
references.citation: Biochem Biophys Res Commun. 2011 Feb 18;405(3):439-44
references.pmid: 21241662
references.citation: Am J Physiol Endocrinol Metab. 2007 Oct;293(4):E986-E1001
references.pmid: 17638705
references.citation: Antioxid Redox Signal. 2005 Jul-Aug;7(7-8):1040-52
references.pmid: 15998259
references.citation: Metabolism. 2008 Aug;57(8):1071-7
references.pmid: 18640384
references.citation: Mol Cell Biol. 2004 Mar;24(5):1844-54
references.pmid: 14966267
references.citation: Hypertension. 2008 Feb;51(2):211-7
references.pmid: 18086956
references.citation: PLoS One. 2012;7(10):e46400
references.pmid: 23082120
references.citation: PLoS One. 2009 Oct 06;4(10):e7293
references.pmid: 19806198
references.citation: Cell. 2011 Sep 30;147(1):185-98
references.pmid: 21962515
references.citation: Antioxid Redox Signal. 2008 Mar;10(3):559-74
references.pmid: 18092937
references.citation: Ann Clin Lab Sci. 2011 Summer;41(3):236-43
references.pmid: 22075506
references.citation: J Appl Physiol (1985). 2009 Aug;107(2):450-9
references.pmid: 19498097
references.citation: Am J Physiol Heart Circ Physiol. 2009 Sep;297(3):H1069-77
references.pmid: 19617406
references.citation: Am J Physiol Endocrinol Metab. 2008 May;294(5):E870-81
references.pmid: 18303120
references.citation: Endocrinology. 2012 May;153(5):2099-111
references.pmid: 22396448
references.citation: J Cell Physiol. 2008 Sep;216(3):796-804
references.pmid: 18446788
references.citation: J Vis Exp. 2009 Oct 19;(32):
references.pmid: 19841615
references.citation: Am J Physiol Renal Physiol. 2005 Jun;288(6):F1191-200
references.pmid: 15727990
references.citation: J Cell Physiol. 2006 Nov;209(2):379-88
references.pmid: 16897752
references.citation: J Clin Invest. 2009 Mar;119(3):573-81
references.pmid: 19188683
references.citation: J Clin Invest. 1988 Aug;82(2):486-94
references.pmid: 3403714
references.citation: Antioxid Redox Signal. 2008 Nov;10(11):1941-88
references.pmid: 18774901
references.citation: Biochem Pharmacol. 2011 Nov 1;82(9):1198-208
references.pmid: 21803028
references.citation: Diabetes. 2013 May;62(5):1519-26
references.pmid: 23274898
references.citation: J Clin Invest. 2004 Dec;114(12):1752-61
references.pmid: 15599400
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Mar;294(3):R673-80
references.pmid: 18094066