Role of NADPH oxidase on beta-cell function and survival after prolonged culture with different glucose concentrations

• Grant number: 13/18232-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 02, 2014
• End date: February 01, 2015
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Angelo Rafael Carpinelli
• Grantee: Arnaldo Henrique de Souza
• Supervisor: Jean-Christophe Jonas
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Universitè Catolique de Louvain (UCL), Belgium
• Associated to the scholarship: 11/21299-9 - EFFECTS OF HYPERGLYCEMIA AND HYPERLIPIDEMIA ON INSULIN SECRETION AND NAD(P)H OXIDASE ACTIVITY IN PANCREATIC ISLETS, BP.DR

Abstract

Oxidative stress has been implicated as a contributor to both the onset and the progression of diabetes and its associated complications. Some of the consequences of increased reactive oxygen species (ROS) production are the development of insulin resistance, beta-cell dysfunction, impaired glucose tolerance, and mitochondrial dysfunction, which can lead ultimately to the diabetic disease state. On the other hand, ROS are described as important molecules during cell signaling and other events such as cell proliferation, apoptosis and insulin secretion. Recently, our group (Dr. Jonas) has characterized the use of new-genetically encoded probes in dynamic and real time measurements, to evaluate ROS production in mitochondria of pancreatic beta cells. The NADPH oxidase activity has been widely recognized as an important source of superoxide in phagocytes (neutrophils and monocytes). Nevertheless, recent studies have suggested that other tissues and cells, such as pancreatic beta-cells, also express NADPH oxidase activity. The role of NADPH oxidase in beta-cells is still unclear, but it has been shown to be involved in the modulation of cellular redox state and glucose stimulated insulin secretion. Thus, the aim of this study is to investigate the role of ROS and NADPH oxidase on beta-cell function and survival after exposure to nutrients. We will first analyze the site of production of ROS during acute and prolonged culture with different glucose concentration and the role of NADPH oxidase will be elucidated using knockout islets for NOX2 subunit. (AU)

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)

DE SOUZA, ARNALDO H.; SANTOS, LAILA R. B.; ROMA, LETICIA P.; BENSELLAM, MOHAMMED; CARPINELLI, ANGELO R.; JONAS, JEAN-CHRISTOPHE. NADPH oxidase-2 does not contribute to beta-cell glucotoxicity in cultured pancreatic islets from C57BL/6J mice. Molecular and Cellular Endocrinology, v. 439, n. C, p. 354-362, JAN 5 2017. (13/18232-5, 11/21299-9)

SANTOS, LAILA R. B.; MULLER, CAROLE; DE SOUZA, ARNALDO H.; TAKAHASHI, HILTON K.; SPEGEL, PETER; SWEET, IAN R.; CHAE, HEEYOUNG; MULDER, HINDRIK; JONAS, JEAN-CHRISTOPHE. NNT reverse mode of operation mediates glucose control of mitochondrial NADPH and glutathione redox state in mouse pancreatic beta-cells. MOLECULAR METABOLISM, v. 6, n. 6, p. 535-547, JUN 2017. (13/18232-5)