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

• Grant number: 09/51893-0
• Support Opportunities: Research Projects - Thematic Grants
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Angelo Rafael Carpinelli
• Grantee: Angelo Rafael Carpinelli
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: 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

Abstract

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)

Scientific publications

(4)

(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, APR 2020. (09/51893-0, 11/04511-4)

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, JAN 2021. (13/08769-1, 17/26339-5, 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., 2020-04-09. (11/04511-4, 09/51893-0)

NUNES MARSIGLIO-LIBRAIS, GABRIELA; APARECIDA VILAS-BOAS, ELOISA; CARLEIN, CHRISTOPHER; HOFFMANN, MARKUS DANIEL ALEXANDER; ROMA, LETICIA PRATES; CARPINELLI, ANGELO RAFAEL. Evidence for NADPH oxidase activation by GPR40 in pancreatic beta-cells. Redox Report, v. 25, n. 1, p. 41-50, JAN 1 2020. (09/51893-0)