MicroRNA-34a contributes to the protective effects of glucagon-like peptide-1 against lipotoxicity in INS-1 cells.
- Author:
Yu-Bing HAN
1
;
Min-Nan WANG
;
Qiang LI
;
Lin GUO
;
Yu-Mei YANG
;
Peng-Jie LI
;
Wei WANG
;
Jin-Chao ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apoptosis; drug effects; Cell Line; Cell Survival; drug effects; Fatty Acids, Nonesterified; toxicity; Glucagon-Like Peptide 1; pharmacology; Insulin-Secreting Cells; cytology; drug effects; metabolism; MicroRNAs; genetics; metabolism; Palmitic Acid; pharmacology; Rats; Real-Time Polymerase Chain Reaction
- From: Chinese Medical Journal 2012;125(23):4202-4208
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDGlucagon-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.
METHODSThe 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.
RESULTSA 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.
CONCLUSIONMicroRNA-34a is involved in the mechanism of GLP-1 on the modulation of beta-cell growth and survival.