Ghrelin regulates insulin resistance by targeting insulin-like growth factor-1 receptor via miR-455-5p in hepatic cells
Objective:To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells.Methods:HepG2 cells were treated with or without Ghrelin(DAG)(1 μmol/L).Glucose consump-tion,intracellular glycogen content,phosphorylation of PI3K and Akt stimulated by insulin,expression of miR-455-5p,as well as IGF-1R protein level were analyzed.In addition,bioinformatic analysis,dual luciferase reporter assay,miR-455-5p mimic or in-hibitor treatment were conducted to investigate the molecular mechanisms.Results:High glucose treatment upregulated miR-455-5p expression but reduced glucose consumption and glycogen content.DAG reversed the effect of high glucose on glu-cose metabolism,increased protein level of IGF-1R and phosphorylation of PI3K/Akt stimulated by insulin,as well as downregu-lated miR-455-5p expression.Bioinformatic analysis indicated IGF-1R was the target of miR-455-5p.Dual luciferase reporter as-say,as well as transfection with miR-455-5p mimic/inhibitor confirmed that DAG activated the IGF-1R/PI3K/Akt signaling via inhibiting miR-455-5p.Conclusion:DAG improves insulin resistance via miR-455-5p-mediated activation of the IGF-1R/PI3K/Akt signaling,suggesting that suppression of miR-455-5p or activation of DAG may be potential targets for T2DM therapy.
国家科技期刊平台
NSTL
万方数据
维普
