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Downregulation of miR-139-5p contributes to the antiapoptotic effect of liraglutide on the diabetic rat pancreas and INS-1 cells by targeting IRS1.
- Source :
-
PloS one [PLoS One] 2017 Mar 27; Vol. 12 (3), pp. e0173576. Date of Electronic Publication: 2017 Mar 27 (Print Publication: 2017). - Publication Year :
- 2017
-
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.
- Subjects :
- Animals
Apoptosis drug effects
Cell Line
Diabetes Mellitus, Experimental drug therapy
Diabetes Mellitus, Experimental genetics
Diabetes Mellitus, Experimental pathology
Down-Regulation
Genetic Therapy
Insulin-Secreting Cells drug effects
Insulin-Secreting Cells metabolism
Insulin-Secreting Cells pathology
Male
Pancreas drug effects
Pancreas metabolism
Pancreas pathology
Rats, Sprague-Dawley
Diabetes Mellitus, Experimental therapy
Hypoglycemic Agents therapeutic use
Insulin Receptor Substrate Proteins genetics
Liraglutide therapeutic use
MicroRNAs genetics
RNAi Therapeutics methods
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 12
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 28346520
- Full Text :
- https://doi.org/10.1371/journal.pone.0173576