title: Downregulation of miR-139-5p contributes to the antiapoptotic effect of liraglutide on the diabetic rat pancreas and INS-1 cells by targeting IRS1.
abstract: Liraglutide is administered as glucagon-like peptide-1 (GLP-1) receptor agonist for diabetic patients and can protect pancreatic β-cells by inhibiting their apoptosis. MicroRNA-139-5p (miRNA-139-5p) participates in the regulation of cancer cell apoptosis. However, it is not clear whether miR-139-5p contributes to the anti-apoptotic effect of liraglutide in β-cells. The objective of the present study was to investigate the role of miR-139-5p on apoptosis of pancreatic β-cells. MicroRNA levels in pancreatic tissue from diabetic rats and INS-1 cells treated with liraglutide were measured by real-time quantitative RT-PCR. The role of miR-139-5p on apoptosis was studied by transfecting INS-1 cells with miR-139-5p mimics. The mRNA and protein expression of the target gene, insulin receptor substrate-1 (IRS1), were measured by qRT-PCR and Western blot, respectively. Apoptosis in rat pancreatic tissue and INS-1 cells was detected by TUNEL and annexin V/propidium iodide costaining. Apoptosis of pancreatic tissue from diabetic rats and INS-1 cells was decreased by administration of liraglutide. The expression of miR-139-5p increased in the pancreas of diabetic rats and decreased with liraglutide treatment. Incubation with liraglutide (100 nM) for 48 h attenuated the expression of miR-139-5p and increased the mRNA and protein levels of IRS1. Direct regulatory effects of miR-139-5p on IRS1 were found by a dual-luciferase reporter assay. Transfection of INS-1 cells with miR-139-5p mimics led to decreases in the mRNA and protein expression of IRS1. In conclusion, our observations suggest that decreased miR-139-5p expression contributes to the anti-apoptotic effect of liraglutide on the diabetic rat pancreas and INS-1 cells by targeting IRS1.
authors.affiliation: Department of Geriatrics, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Geriatrics, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Geriatrics, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Gong
authors.affiliation: Department of Geriatrics, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Mei-Lin
authors.initials: ML
authors.lastname: Ding
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Shu-Bin
authors.initials: SB
authors.lastname: Hong
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Hai-Peng
authors.initials: HP
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D015536:Down-Regulation; D015316:Genetic Therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000069450:Liraglutide / Q000627:therapeutic use*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000067492:RNAi Therapeutics / Q000379:methods; D017207:Rats, Sprague-Dawley
chemical_list: D007004:Hypoglycemic Agents; D055504:Insulin Receptor Substrate Proteins; C000600035:MIRN139 microRNA, rat; D035683:MicroRNAs; D000069450:Liraglutide