The role of NAD(P)H oxidase in the physiological and pathological molecular mechanisms of insulin secreting cells

• Grant number: 13/08769-1
• Support Opportunities: Research Projects - Thematic Grants
• Start date: June 01, 2014
• End date: May 31, 2018
• 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: Aparecida Emiko Hirata ; Fernando Rodrigues de Moraes Abdulkader
• Associated researchers: Fernanda Ortis ; Lucia Rossetti Lopes ; Luiz Roberto Giorgetti de Britto ; Rui Curi
• Associated research grant(s): 14/14574-1 - Multi-User Equipment approved in grant 13/08769-1: imaging system for optical measurements of the redox state and membrane potential, AP.EMU
• Associated scholarship(s): 15/00446-4 - Metabolic regulation, and insulin secretion and action mechanism induced by L-glutamine supplementation in mutant obese mice, BP.PD

Abstract

We intend to further study the role of NAD(P)H oxidase in the physiology and pathophysiology of insulin-secreting cells. The high point of this project will be the implementation of more advanced research methods in order to access information not yet available and thus, confirm which free radical is produced and in which cytosolic compartment. Therefore, we will use genetically modified sensors (adenoviral vectors) in cultured pancreatic rat islets and insulin secreting cell lines and also implement studies with islets from knockout mice for the gp91phox (gp91phox-/-) and p47phox (p47phox-/-) subunits of NAD(P)H oxidase. Thus, we intent to elucidate the role of NADP)H oxidase in insulin secretion stimulated by glucose and fatty acids; investigate whether the modulation of membrane composition promoted by HDL would have consequences in the activation of NADPH oxidase; evaluate whether the excessive intake of fat and sucrose alters NAD(P)H oxidase ROS production; investigate the pathways involved in the protective effect of EPA and DHA in the INS-1E cell line and in pancreatic islets (primary culture) chronically exposed to saturated fatty acids and AGEs; to investigate the electrical coupling between the excitable cells of pancreatic islets isolated from different species; evaluate whether NAD(P)H oxidase supplies NAD+ for the proper functioning of glycolysis; evaluate the effect of the blockade of the renin-angiotensin system (RAS) on the activity of NAD(P)H oxidase in isolated pancreatic islets in diabetic animals / obese (ob / ob) and possible involvement of the NAD(P)H oxidase on reticulum stress and the expression of TLRs in pancreatic islets isolated from diabetic obese mice (ob / ob). (AU)

Scientific publications

(5)

(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)

SIMOES, DANIEL; RIVA, PATRICIA; PELICIARI-GARCIA, RODRIGO ANTONIO; CRUZAT, VINICIUS FERNANDES; GRACIANO, MARIA FERNANDA; MUNHOZ, ANA CLAUDIA; TANEDA, MARCO; CIPOLLA-NETO, JOSE; CARPINELLI, ANGELO RAFAEL. Melatonin modifies basal and stimulated insulin secretion via NADPH oxidase. Journal of Endocrinology, v. 231, n. 3, p. 235-244, DEC 2016. (13/08769-1)

REBELATO, EDUARDO; SANTOS, LAILA R.; CARPINELLI, ANGELO R.; RORSMAN, PATRIK; ABDULKADER, FERNANDO. Short-term high glucose culture potentiates pancreatic beta cell function. SCIENTIFIC REPORTS, v. 8, AUG 30 2018. (13/08769-1, 14/14826-0)

VILAS-BOAS, ELOISA A.; CARLEIN, CHRISTOPHER; NALBACH, LISA; ALMEIDA, DAVIDSON C.; AMPOFO, EMMANUEL; CARPINELLI, ANGELO R.; ROMA, LETICIA P.; ORTIS, FERNANDA. Early Cytokine-Induced Transient NOX2 Activity Is ER Stress-Dependent and Impacts beta-Cell Function and Survival. ANTIOXIDANTS, v. 10, n. 8, AUG 2021. (17/26339-5, 20/06184-0, 17/04580-2, 13/08769-1)

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)

DE JESUS, DANIEL SIMOES; BARGI-SOUZA, PAULA; CRUZAT, VINICIUS; YECHOOR, VIJAY; CARPINELLI, ANGELO RAFAEL; PELICIARI-GARCIA, RODRIGO ANTONIO. BMAL1 modulates ROS generation and insulin secretion in pancreatic beta-cells: An effect possibly mediated via NOX2. Molecular and Cellular Endocrinology, v. 555, p. 8-pg., 2022-09-15. (13/08769-1)