title: MicroRNA-34a contributes to the protective effects of glucagon-like peptide-1 against lipotoxicity in INS-1 cells.
abstract: 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.
  
  
  CONCLUSIONS
  MicroRNA-34a is involved in the mechanism of GLP-1 on the modulation of beta-cell growth and survival.
authors.affiliation: Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Yu-Bing
authors.initials: YB
authors.lastname: Han
authors.forename: Min-Nan
authors.initials: MN
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Yang
authors.forename: Peng-Jie
authors.initials: PJ
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jin-Chao
authors.initials: JC
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000633:toxicity*; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019308:Palmitic Acid / Q000494:pharmacology; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D005230:Fatty Acids, Nonesterified; C560944:MIRN34 microRNA, rat; D035683:MicroRNAs; D019308:Palmitic Acid; D052216:Glucagon-Like Peptide 1