Background Glucagon-like peptide-1 （GLP-1） reduces fatty acid-induced beta-cell lipotoxicity in diabetes; however, the explicit mechanisms underlying this process are not fully understood. This study was designed to investigate the involvement of microRNA, which regulates gene expression by the sequence-specific inhibition of mRNA transcription in the GLP-1 mediation of beta-cell function. Methods The cell viability and apoptosis were determined using an methyl thiazoleterazolium （MTT） assay and flow cytometry. The expression of genes involved in beta-cell function, including microRNA-34a and sirtuin 1, were investigated using real-time PCR. The underlying mechanisms of microRNA-34a were further explored using cell-transfection assays. Results A 24-hours incubation of INS-1 cells with palmitate significantly decreased cell viability, increased cell apoptosis and led to the activation of microRNA-34a and the suppression of sirtuin 1. A co-incubation with GLP-1 protected the cells against palmitate-induced toxicity in association with a reduction in palmitate-induced activation of microRNA-34a. Furthermore, palmitate-induced apoptosis was significantly increased in cells that were infected with microRNA-34a mimics and decreased in cells that were infected with microRNA-34a inhibitors. Conclusion MicroRNA-34a is involved in the mechanism of GLP-1 on the modulation of beta-cell growth and survival.
HAN Yu-bingWANG Min-nanLI QiangGUO LinYANG Yu-meiLI Peng-jieWANG WeiZHANG Jin-chao
