GLP-1 Agonists Liraglutide Improved Vascular Endothelial Function in Type 2 Diabetes Rats

Diabetes Research: Open Access

Li X¹, Wu W³, Wang Y¹, Zhang X³, Feng X⁴, Liu R^2*

¹Department of physiology, Renji College, Wenzhou Medical University, Wenzhou 325035, China ²Department of Anesthesiology, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China ³Department of Anesthesiology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China ⁴Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, 07103, USA

Corresponding Author: Ruohai Liu Address: Department of Anesthesiology, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China; E-mail: liuruohai@163.com Received date: 11 July 2020; Accepted date: 25 July 2020; Published date: 08 August 2020

Citation: Li X, Wu W, Wang Y, Zhang X, Feng X, Liu R. GLP-1 Agonists Liraglutide Improved Vascular Endothelial Function in Type 2 Diabetes Rats. Diab Res Open Access. 2020 Aug 08;2(2):46-55.

Copyright © 2020 Li X, Wu W, Wang Y, Zhang X, Feng X, Liu R. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords: Oxidative Stress, Liraglutide, Glucagon-like Peptide-1 Receptor, Type 2 Diabetes, Endothelial Oxide Synthase

Abstract

Objective: Liraglutide (LIRA), a Glucagon-like peptide-1 (GLP-1) receptor agonist, showed potential vascular protective effects with the mechanism remained incompletely understood. Therefore, this study aimed to investigate whether LIRA exerts its effect on vascular endothelial function in rats with type 2 diabetes mellitus (T2DM) via caveolin-1/ endothelial oxide synthase (eNOS) expression.

Methods: T2DM rats were used as study subjects and randomly divided into four groups: 1) Veh group, 2) Veh+LIRA group, 3) T2DM group, and 4) T2DM+LIRA group. All rats received either saline or LIRA 0.2 mg/kg (by i.p. injection) per day for 4 weeks. After the model was successfully established, vascular endothelial function was determined the effect of vasodilator to mesenteric artery rings. Immunofluorescence and western blot were performed to understand the molecular mechanism. Cultured HUVECs with small interfering RNA (siRNA) under high glucose (HG), NO concentration, and western blot were performed to understand the molecular mechanism between LIRA and vascular endothelial function.

Results: Based on our results, the LIRA reduced hyperglycemia and ameliorated vascular endothelial dysfunction in type 2 diabetic mice. LIRA activated eNOS phosphorylation, suppressing oxidative stress and enhancing endothelium-dependent vasorelaxation of mesenteric arteries. Besides, from its anti-oxidative capacity, LIRA activated eNOS to dilate the mesenteric arteries via the downregulation of Cav-1.

Conclusion: LIRA ameliorates vascular endothelial dysfunction in rats with type 2 diabetes mellitus via anti-oxidative and activated eNOS by downregulated Cav-1.