Effect of dexamethasone on the expression of miRNA in the endocrine pancreas in pregnant rats

Abstract

In the last decade the complex regulation of gene expression is increased after the discovery of microRNA (miRNA). miRNA are small non-coding RNAs (20-30 nucleotides long) widely expressed in multicellular organisms. In mammals, miRNAs act mainly as repressors of translation. Recent works suggest that miRNA play direct roles in insulin secretion regulation, in the development of the endocrine pancreas and in beta cells differentiation. Together, these evidences indicate that miRNA can modulate plasma glucose and are probably involved in the pathogenesis of diabetes mellitus (DM). It is well known the relationship among pregnancy, diabetogenic hormones and alterations in glucose homeostasis that may lead to DM2. Among these are glucocorticoids, which alter both the secretion and action of insulin in target tissues by mechanisms not completely understood. Thus, this project aims to evaluate the effects of treatment with dexamethasone (DEX) at the end of pregnancy in rats on the expression of miRNA in pancreatic islets. Isolated islets will be used for large-scale analysis of miRNA expression. Putative miRNA targets will be screened in databases and validated by overexpression / blocking of DEX-regulated miRNA. Thus, we expected to identify early targets to allow future studies of therapeutic strategies before the onset of DM2.