Analysis of death, proliferation and differentiation of ß-cells in an animal model of Type 1 Diabetes Mellitus submitted to physical training

• Grant number: 18/16999-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2018
• End date: June 30, 2019
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Fernanda Ortis
• Grantee: Catharina de Barros Pimentel Villaça
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Type 1 Diabetes mellitus (DM1) is a pathology that occurs due to autoimmune destruction of pancreatic ß cells, initially without clinical manifestations. This autoimmune response is mediated by different proinflammatory cytokines secreted by an islet immune cell infiltrate, such as interleukin (IL) 1ß, interferon (IFN) and tumor necrosis factor (TNF), in process known as insulitis. In response to this pro-inflammatory environment, the ß-cell activates several signaling pathways, both pro- and anti-apoptotic, with prevalence of the pro-apoptotic pathways. Intracellular ß-cell signaling in response to stimulation by proinflammatory cytokines has been demonstrated in cells cultured in vitro by various groups, including ours. However, in the last decade the signaling in the microenvironment of the islet of Langerhans has received great notoriety, since it is directly related to the function of the different cell types contained therein, and alterations in the islet structure can contribute to the impairment in the function of the ß-cell. The physical exercise in mice with DM1 leads to a reduction in the infiltration of immunological cells in the islet, as well as the expression of IL-6, which in this context seems to have an anti-inflammatory character, besides decreasing the expression of pro-inflammatory cytokines, such as TNF-alpha. It was also observed that mice with DM1 undergoing medium intensity exercise present a reduction in markers of oxidative stress in the ß-cell compared to the control group. Despite this, little is known about the effects of exercise on preventing the damage of beta cell death induced during DM1. Thus, the aim of this study is to analyze the effect of physical exercise on the proliferation, death and differentiation of ß cells in animals with DM1 induced by multiple and low doses of streptozotocin through the immunohistochemical labeling, thus considering the important effect of microenvironment and structure in the proinflammatory signaling.