Evidence for the involvement of GPR40 and NADPH oxidase in palmitic acid-induced superoxide production and insulin secretion

Autor(es)

Graciano, Maria Fernanda ^[1] ; Valle, Maira Mello ^[1] ; Curi, Rui ^[1] ; Carpinelli, Angelo Rafael ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ISLETS; v. 5, n. 4, p. 139-148, JUL 1 2013.
• Citações Web of Science: 13

Resumo

G protein coupled receptor 40 (GPR40) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex have been shown to be involved in the fatty acid amplification of glucose-stimulated insulin secretion (GSIS). The effect of palmitic acid on superoxide production and insulin secretion by INS-1E cells and the possible involvement of GPR40 and NADPH oxidase in these processes were examined in this study. Cells were incubated during 1 h with palmitic acid in low and high glucose concentrations, a GPR40 agonist (GW9508) and inhibitors of NADPH oxidase (diphenyleneiodonium, DPI) and PKC (calphostin C). GW9508 induced superoxide production at 2.8 and 5.6 mM glucose concentrations and stimulated insulin secretion at 16.7 mM glucose concentration involving both PKC and NADPH oxidase activation. Palmitic acid induced superoxide production through NADPH oxidase and GPR40-dependent pathways and the stimulation of insulin secretion in the presence of a high glucose concentration was reduced by knockdown of GPR40 using siRNA. Our results suggest that palmitic acid induces superoxide production and potentiates GSIS through NADPH oxidase and GPR40 pathways in pancreatic cells. (AU)

• Processo FAPESP: 10/52184-0 - Avaliacao da secrecao de insulina e especies reativas de oxigenio e nitrogenio por acidos graxos em linhagem ins-1e.
• Beneficiário: Maria Fernanda Rodrigues Graciano
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 05/57946-7 - Mecanismos de ação do palmitato como modulador da NAD(P)H oxidase em ilhotas pancreáticas
• Beneficiário: Maria Fernanda Rodrigues Graciano
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto