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| Author(s): |
Maria Fernanda Rodrigues Graciano
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2011-03-01 |
| Examining board members: |
Angelo Rafael Carpinelli;
Everardo Magalhães Carneiro;
Carla Roberta de Oliveira Carvalho;
Anna Karenina Azevedo Martins;
Silvana Auxiliadora Bordin da Silva
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| Advisor: | Angelo Rafael Carpinelli |
| Abstract | |
The NADPH oxidase complex is involved in the glucose-stimulated insulin secretion and the superoxide production in pancreatic islets. In this study, we examined the effect of palmitic acid on superoxide production and insulin secretion by rat pancreatic islets and INS-1E cells. Palmitate increased superoxide production in a process dependent on the activation of PKC, NADPH oxidase and fatty acid oxidation. In fact, palmitate caused p47PHOX translocation to the plasma membrane. Exposure to palmitate for 1 h up-regulated the protein content of p47PHOX and the mRNA levels of p22PHOX, gp91PHOX, p47PHOX, proinsulin and the GPR40. Fatty acid stimulation of insulin secretion in the presence of a high glucose concentration was reduced by the inhibition of NADPH oxidase activity and by the inhibition of GPR40 expression by a small interference RNA. In conclusion, NADPH oxidase is an important source of palmitate-induced superoxide production in beta cells. The NADPH oxidase activity and GPR40 signaling are involved in the control of insulin secretion by palmitate. (AU) | |
| FAPESP's process: | 05/57946-7 - Mechanisms of palmitate action as a modulator of NAD(P)H oxidase in pancreatic islets |
| Grantee: | Maria Fernanda Rodrigues Graciano |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |