Haipeng Xiao
Sun Yat-sen University, China
Title: Down-regulation of miR-139-5p contributes to the anti-apoptotic effect on diabetic rat islets and INS1 cells induced by Liraglutide via targeting Irs1
Biography
Biography: Haipeng Xiao
Abstract
Diabetes is a chronic metabolic disease characterized with elevated glucose and lipid disturbance, which pathogenesis involves beta cell dysfunction and insulin resistance. Liraglutide is administered as GLP-1 receptor agonist on patient with diabetes mellitus and shows protective effect on beta cell function by inhibiting its apoptosis and promoting its proliferation and regeneration. MicroRNAs (miRNAs) are a category of endogenous non-coding small RNA, which inhibit the translation by binding to the 3’ untranslated region (3’ UTR) of their target mRNAs. It has become increasingly clear that miRNAs are not only involved in regulation of cell differentiation and apoptosis, but also in the pathogenesis of a variety of diseases. In our study, we aim to investigate the miRNA level differentially expressed in the pancreatic tissues of normal or diabetic SD rats without or with administration of Liraglutide, screen intended miRNA and predict its target gene，and explore the mechanism by which miRNA contributes to the anti-apoptotic effect of Liraglutide on pancreatic beta cells. We revealed differential expression of miRNAs and validated the increased expression of miR-139-5p in diabetic rats, while which decreased in diabetic rats with administration of liraglutide. We verified the direct regulatory effect of miR-139-5p on insulin receptor substrate 1(Irs1), a key player in insulin signal transduction pathway, through the target sequence ACTGTAG by using double luciferase report experiments. We also found palmitic acid can increase the expression of miR-139-5p and reduce IRS1 expression at both mRNA level and protein level in INS1 cells. Furthermore, administration of Liraglutide decreased the expression of miR-139-5p and enhanced the expression of IRS1, which protected both pancreatic tissues of SD rats and INS1 cells from apoptosis. Our data demonstrates that increased expression of miR-139-5p, which targets Irs1, prompts apoptosis in both pancreatic tissue of diabetic SD rats and INS1 cells treated with palmitic acid, down-regulation of miR-139-5p contributes to the anti-apoptotic effect induced by Liraglutide via targeting Irs1.