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EFFECTS OF HYPERGLYCEMIA AND HYPERLIPIDEMIA ON INSULIN SECRETION AND NAD(P)H OXIDASE ACTIVITY IN PANCREATIC ISLETS

Grant number: 11/21299-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2012
Effective date (End): May 31, 2016
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal Investigator:Angelo Rafael Carpinelli
Grantee:Arnaldo Henrique de Souza
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:09/51893-0 - The role of NAD(P)H oxidase in the molecular mechanisms of pancreatic beta cell physiology, AP.TEM
Associated scholarship(s):13/18232-5 - Role of NADPH oxidase on beta-cell function and survival after prolonged culture with different glucose concentrations, BE.EP.DR

Abstract

The pancreatic islets are composed mostly of B cells that secrete insulin, and have their function modulated by the concentration of nutrients present in the circulation, including, glucose, recognized as the major insulin secretagogue. Metabolic disorders such as metabolic syndrome, obesity and insulin resistance are characterized by an imbalance in glucose homeostasis and deficiency in the secretion and / or action of this hormone, produced by B cells such disorders are provided by food intake and consequently calorie, high serum concentration of fatty acids (FA), which causes accumulation of lipids in tissue, insulin resistance, hyperinsulinemia and hyperglycemia. The FA can cause excessive damage to the B cell, which are caused by the accumulation of metabolites derived from these fatty acids. Besides this, the increase in plasma glucose concentration leads to disorders that have been attributed to a deviation in the direction of metabolic substrate associated with excessive formation of advanced glycation end products (AGE) and reactive oxygen species (ROS). Increased circulating AGEs is associated with complications in diabetes mellitus (DM) and even the very origin of the disease. The formation of ROS results in excessive stress caused by the high oxidation rate, called oxidative stress, which is related to the loss of pancreatic B cell function. An example of cellular production of ROS, is catalyzed by the enzyme nicotinamide adenine dinucleotide phosphate oxidase (NAD(P)H oxidase). In this sense, the imbalance in glucose homeostasis correlates with increased circulating AGEs and ROS. The glycated albumin is an important marker of glycemic control in DM. Although the advanced glycation of albumin in vitro was used as a model to study the functionality of the B cell pancreatic, no one knows the counterpart of in vivo vs. production. AGEs in vitro imbalance that occurs in blood glucose levels. Additionally, little is known about the effects of advanced glycation on pancreatic islets and so little on the enzyme NAD(P)H oxidase and ROS. The objective of this study is to induce the glucose imbalance and investigate the effects on the production of ROS, metabolism and function of isolated pancreatic islets, as well as evaluating the expression and activity of the enzyme NAD(P)H oxidase in pancreatic B cells. It also aimed to examine whether AGEs are potential modulators of this enzyme in cells that secrete insulin.

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. Web of Science Citations: 10.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SOUZA, Arnaldo Henrique de. Redox modulation, function and survival of pancreatic β-cells: evidence on the role of NADPH oxidase-2 (NOX2) enzyme in a model of glucotoxicity in vitro.. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas São Paulo.

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