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Acute and chronic effects of oleic and palmitic acids and the agonist GW9508 on insulin secretion and oxidative stress of the lineage BRIND-BD11

Grant number: 11/04511-4
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): August 01, 2011
Effective date (End): June 30, 2013
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Angelo Rafael Carpinelli
Grantee:Eloisa Aparecida Vilas Boas
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The plasmatic concentration of glucose is the main insulin secretion modulator, hormone produced and secreted from pancreatic islets beta cells. However, other nutrients, such as fatty acids, are also capable of modulating this secretion, through mechanisms still not elucidated. The fatty acids effects in insulin secretion and in the beta cell normal function are controversial. Acutely, they are capable of stimulating insulin secretion and chronically cause desensitization and even cell death. Fatty acids intracellular metabolism through beta-oxidation is an important route responsible for the insulin secretion stimulation by fatty acids. It has been recently identified, in pancreatic beta cells, the GPR-40, G-protein-coupled receptor activated by long chain fatty acids, saturated or unsaturated, which represents another important regulatory route for the insulin secretion process. The production of reactive oxygen species by fatty acids influences the insulin secretion, the oxidative stress and beta cell normal function. The aim of this project is to evaluate the acute and chronic effects of oleic and palmitic acids, and the agonist of GPR-40 GW9508, in the insulin secretion, in the reactive oxygen species (total and mitochondrial) production and in the endoplasmic reticulum stress, analyzing the GPR-40 route and the fatty acids metabolism in these processes. In this study we will be using BRIN-BD11 cells, cellular lineage which possesses the same characteristics of insulin synthesis and secretion as normal beta cells. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VILAS-BOAS, ELOISA APARECIDA; KARABACZ, NOEMIE; MARSIGLIO-LIBRAIS, GABRIELA NUNES; REZENDE VALLE, MAIRA MELO; NALBACH, LISA; AMPOFO, EMMANUEL; MORGAN, BRUCE; CARPINELLI, ANGELO RAFAEL; ROMA, LETICIA PRATES. Chronic activation of GPR40 does not negatively impact upon BRIN-BD11 pancreatic beta-cell physiology and function. PHARMACOLOGICAL REPORTS, v. 72, n. 6, SI, . (09/51893-0, 11/04511-4)
VILAS-BOAS, ELOISA APARECIDA; KARABACZ, NOEMIE; MARSIGLIO-LIBRAIS, GABRIELA NUNES; REZENDE VALLE, MAIRA MELO; NALBACH, LISA; AMPOFO, EMMANUEL; MORGAN, BRUCE; CARPINELLI, ANGELO RAFAEL; ROMA, LETICIA PRATES. Chronic activation of GPR40 does not negatively impact upon BRIN-BD11 pancreatic beta-cell physiology and function. PHARMACOLOGICAL REPORTS, v. 72, n. 6, p. 13-pg., . (11/04511-4, 09/51893-0)
VILAS-BOAS, ELOISA APARECIDA; NALBACH, LISA; AMPOFO, EMMANUEL; LUCENA, CAMILA FERRAZ; NAUDET, LEA; ORTIS, FERNANDA; CARPINELLI, ANGELO RAFAEL; MORGAN, BRUCE; ROMA, LETICIA PRATES. Transient NADPH oxidase 2-dependent H2O2 production drives early palmitate-induced lipotoxicity in pancreatic islets. Free Radical Biology and Medicine, v. 162, . (13/08769-1, 17/26339-5, 09/51893-0, 11/04511-4)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
BOAS, Eloisa Aparecida Vilas. Chronic treatment with palmitic acid increases superoxide content and apoptosis of BRIN-BD11 cells with participation of NADPH oxidase, without GPR40 involvement.. 2013. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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