Effect of the exercise training on the nitric oxide production in pancreatic islets of trained mice exposed to streptozotocin and inflammatory cytokines: cross talk between skeletal muscle and endocrine pancreas

• Grant number: 13/03365-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2013
• End date: May 31, 2016
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Antonio Carlos Boschiero
• Grantee: Flavia Maria Moura de Paula
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 14/17105-2 - Effect of exercise training on the endoplasmatic reticulum stress, inflammation and apoptotic pathways in pancreatic ² cells, BE.EP.PD

Abstract

During the onset of type 1 diabetes, the apoptosis of beta cell is mediated by the activation of cellular death pathways and generation of reactive oxygen and nitrogen species, damaging these cells. Nitric oxide, formed by the activation of inducible nitric oxide sintase, promotes endoplasmatic reticulum stress, nitrozilation and proteassome degradation of anti-apoptotic proteins and activation of pro-apoptotic proteins, leading to beta cell apoptosis. In healthy animals, exercise training acts on endocrine pancreas activating the proliferation and growth pathways. However, the effect of exercise on the modulation of nitric oxide production in islets, during the development of type 1 diabetes, is poorly understood. The aim of this project is to clarify the molecular mechanisms of prevention of beta cell apoptosis by exercise, during the progression of type 1 diabetes. We will center our attention on the activation of survival pathways (eNOS; PI3K/AKT; ERK1/2) and blockage of death pathways (NFkB/iNOS; JNK; DP5/PUMA/Bim), specially the effect of nitric oxide on the intracellular signaling. In addition, the action of possible molecules involved in the cross talk between skeletal muscle and endocrine pancreas, possibly responsible for the modulations on the intracellular pathways in pancreatic islets during exercise training, will be analyzed. (AU)