期刊
PEERJ
卷 7, 期 -, 页码 -出版社
PEERJ INC
DOI: 10.7717/peerj.6567
关键词
Endothelial function; Diabetes; Apoptosis; Liraglutide; miRNA
资金
- National Key R&D Program of China [2017YFC1309603]
- National Key Research and Development Program of China [2016YFA0101002]
- Medical Epigenetics Research Center
- Chinese Academy of Medical Sciences [2017PT31036, 2018PT31021]
- Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2017PT32020, 2018PT32001]
- National Natural Science Foundation of China [81170736, 81570715, 81870579, 81870545]
- National Natural Science Foundation for Young Scholars of China [81300649]
- China Scholarship Council foundation [201308110443]
- PUMC Youth Fund [33320140022]
- Fundamental Research Funds for the Central Universities
- Scientific Activities Foundation for Selected Returned Overseas Professionals of Human Resources and Social Security Ministry
Background and Aims: Many studies have revealed that glucagon-like peptide-1 has vasoprotective effects. In this study, we investigated whether liraglutide suppressed endothelial dysfunction and explored the mechanism involved. Methods: Experimental diabetes was induced through combined high-fat diet administration and intraperitoneal streptozotocin injections. Rats were randomly divided into the following four groups: control, diabetes, diabetes + a low liraglutide dose (0.2 mg/kg/d), and diabetes + a high liraglutide dose (0.4 mg/kg/d). Endothelial function and metabolic parameters were measured after 8 weeks of treatment. miRNA arrays were analyzed to identify the differentially expressed miRNAs. Results: We found that liraglutide significantly improved aortic endothelial function in diabetic rats. Liraglutide inhibited miR-93-5p, miR-181a-5p and miR-34a-5p expression, and activated miR-26a-5p expression. miRNA mimic transfection experiments indicated negative relationships between miR-93-5p, miR-181a-5p, miR-34a-5p, and miR-26a-5p and Sirt1, Creb, Bcl-2, and Pten expression, respectively. Moreover, liraglutide increased Sirt1, Creb, and Bcl-2 expression levels and reduced Pten expression level. Conclusion: Our results demonstrate the role of key miRNAs in the liraglutide-mediated regulation of endothelial cell function in diabetic rats.
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