A glucagon-like peptide-1 analog, liraglutide, ameliorates endothelial dysfunction through miRNAs to inhibit apoptosis in rats

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.