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The role of NAD(P)H oxidase in the molecular mechanisms of pancreatic beta cell physiology

Grant number: 09/51893-0
Support type:Research Projects - Thematic Grants
Duration: December 01, 2009 - November 30, 2013
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Angelo Rafael Carpinelli
Grantee:Angelo Rafael Carpinelli
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Co-Principal Investigators:Carla Roberta de Oliveira Carvalho
Associated scholarship(s):12/16374-4 - Possible protective effects of EPA and DHA against apoptosis induced by palmitate in pancreatic islets in culture, BP.DR
11/21299-9 - Effects of hyperglycemia and hyperlipidemia on insulin secretion and NAD(P)H oxidase activity in pancreatic islets, BP.DR
11/18993-0 - Identification and localization of reactive oxygen species during nutrient-induced insulin secretion: role of NADPH oxidase, BP.PD
11/08172-0 - Participation of clock genes in the insulin secretion process in BRIN-BD11 cell line, BP.DR
10/09254-7 - Evaluation of the expression of components of NAD (p) h oxidase in muscle, liver and adipose tissue in an experimental model of insulin resistance after treatment with losartan, BP.IC


We have previously shown that pancreatic beta cells express the superoxide-producing enzyme NAD(P)H oxidase and that the decrease in its activity importantly impairs glucose metabolism, intracellular calcium oscillations and glucose-stimulated insulin secretion (GSIS). Chronic exposure to fatty acids or interleukins induce changes in the insulin secretion mechanisms that are partially due to modulation of NAD(P)H oxidase activity. Angiotensin II (Ang II) via AT1 receptor activates NAD(p)H oxidase in isolated pancreatic islets thus modulating insulin secretion. Preliminary data from our laboratory show that hydrogen peroxide (H202) production is dramatically reduced after NAD(p)H oxidase inhibition. We also have strong evidence suggesting that pentose-phosphate pathway activation in GSIS has a pivotal role in the maintenance of the redox environment of pancreatic beta cells. There is also evidence that NADPH oxidase participates in the development of insulin resistance in aging, what can be partially reversed by dehydropiandrosterone (DHEA) treatment. Thus, we intend to focus our studies in the role of NAD(P)H oxidase and H202 in the cellular mechanisms which couple glucose metabolism to insulin and glucagon secretion and the participation of Ang II, DHEA, melatonin and ethanol in the regulation of the activity of this enzyme. BRIN BD11 and INS1E cells, which possess physiological characteristics similar to rat beta cells will be also used. (AU)