Molecular mechanisms involved in exercise training-induced adaptations on insulin secretion: a role for the ß-cell redox status

• Grant number: 15/13929-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 01, 2015
• End date: June 30, 2016
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Everardo Magalhães Carneiro
• Grantee: Nayara de Carvalho Leite
• Supervisor: Jean-Christophe Jonas
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Universitè Catolique de Louvain (UCL), Belgium
• Associated to the scholarship: 13/00750-0 - MODULATION OF INSULIN SECRETION BY METABOLIC COUPLING FACTORS (MCFs) IN PANCREATIC ISLETS FROM UNDERNOURISHED OBESE MICE: A ROLE FOR CHRONIC EXERCISE., BP.DR

Abstract

Regular exercise is one of the key elements in the treatment of obesity. Although the metabolic actions of the exercise in insulin sensitive tissues are well known, the effects of exercise on the endocrine pancreas remain poorly understood. Trained animals show a lower response to glucose-induced insulin secretion. Glucose metabolism provides coupling factors, which modulate metabolic networks, and are involved in the triggering and amplification of fuel induced insulin secretion. Inhibition of various complexes of the electron transport chain (ETC) abolishes glucose induced insulin secretion, and there is ample evidence that the mitochondrial ETC plays a role in generating additional signals for secretion in addition to ATP. Uncoupling protein 2 (UCP2) and mitochondrial Stat3 were shown to regulate ETC activity. Exercise training increases the expression of UCP2, and Stat3 phosphorylation. Both mechanisms, alone or together, might be modulating ETC and ROS production. We hypothesized that mStat3 and/or UCP2 modulation of ROS production are closely linked to the reduction of GIIS reported after exercise training. In this sense our goals are (1) Elucidate the main sites of intracellular hydrogen peroxide production as well as the mechanisms that correlate UCP2 and/or STAT3 and the production of ROS. (2) Investigate if pancreatic ² cell and skeletal muscle signaling might, at least in part, be due to contraction-released IL-6. (AU)