Evaluation of the secretory response in vivo and in vitro in rat and mice islets treated with dexamethasone

• Grant number: 10/05196-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2010
• Effective date (End): July 31, 2013
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Antonio Carlos Boschiero
• Grantee: Andre Otavio Peres Protzek
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The use of steroids as a way to induce peripheral insulin resistance (IR) is based on validated approach in the literature, as well as sparking particular practical interest, since the use of this class of substances in medical routine. As an IR, induced by administration of dexamethasone, there is an increase in circulating levels of insulin as a result of increased insulin secretion by pancreatic islets. This process is known as ²-cell compensation and allows the proper maintenance of glucose homeostasis. The model drug (dexamethasone) IR is used to induce hyperfunction of ² cells in rats and humans. However, the hyperfunction of ² cells does not occur in mice subjected to the same protocol performed in experimental models with rats. In mice there is a reduction of circulating levels of insulin. Thus, the results are controversial and secretory response appears to be similar between rats and humans, but differently in mice. Still, the variation of dose and administration time contributes to the diversity of results observed. Thus, the proposal of the current project, we intend to clarify and compare the major adaptations that occur in the endocrine pancreas in two animal models, rats and mice treated with a fixed dose and duration of dexamethasone in order to establish mechanisms that are common with each other or not, underlying the changes observed in each animal model. Still, we find mechanisms by which gives the direct effect of dexamethasone on islets isolated from both species. To do this, parameters such as body growth, food intake, blood parameters and serum, peripheral sensitivity to insulin and glucose, insulin secretion, ² cell proliferation, kinomic profile analysis and quantification of mRNA and proteins involved in insulin secretion process will be investigated.