title: Omega-3 fatty acids control productions of superoxide and nitrogen oxide and insulin content in INS-1E cells.
abstract: Omega-3 fatty acids have multiple effects in peripheral tissues and pancreatic beta cell function. Dietary depletion of omega-3 fatty acids is associated with pancreatic islet dysfunction and insulin resistance in rats. Herein, the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on pancreatic beta cell redox state and function were investigated. INS-1E insulin-secreting cells were incubated with EPA and DHA in combination with palmitic acid, and productions of reactive oxygen species (ROS), nitric oxide (NO) and insulin were measured. The involvement of the NADPH oxidase complex in ROS production and expression of the antioxidant enzymes was also investigated. After incubation for 1 or 48 h, productions of superoxide (by hydroethidine method), nitric oxide (by 4,5-diaminofluorescein diacetate-DAF-2DA assay), insulin (by radioimmunoassay), and expressions (by western blot analysis) of glutathione peroxidase (GPx-1) and gp91PHOXwere measured. EPA and DHA reduced superoxide production after 1-h incubation. After 48 h, palmitic acid reduced superoxide production that was normalized by EPA treatment. Palmitic acid increased NO production that was reverted by EPA and DHA. Palmitic acid increased insulin secretion after 48 h, whereas both omega-3 fatty acids increased intracellular insulin content. EPA and DHA enhanced GPx-1 expression as well as gp91PHOXglycosylated form. In conclusion, EPA and DHA increased intracellular insulin content and antioxidant enzymatic defense capacity and decreased pro-oxidant generating activities that are associated with maintenance of pancreatic beta cell redox state in response to palmitic acid.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil. mafegraciano@uel.br.|Department of Physiological Sciences, State University of Londrina (UEL), Londrina, Paraná, Brazil. mafegraciano@uel.br.
authors.forename: M F
authors.initials: MF
authors.lastname: Graciano
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.|Department of Physiological Sciences, State University of Londrina (UEL), Londrina, Paraná, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Leonelli
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Curi
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: R Carpinelli
mesh_terms: D000818:Animals; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000819:agonists / Q000096:biosynthesis*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019308:Palmitic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D007328:Insulin; D008562:Membrane Glycoproteins; D013481:Superoxides; D004281:Docosahexaenoic Acids; D019308:Palmitic Acid; D009569:Nitric Oxide; D015118:Eicosapentaenoic Acid; D005979:Glutathione Peroxidase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat
keywords: Docosahexaenoic acid; Eicosapentaenoic acid; Fish oil; Insulin secretion; Palmitic acid; Pancreatic islets