Dulaglutide restores endothelial progenitor cell levels in diabetic mice and mitigates high glucose-induced endothelial injury through SIRT1-mediated mitochondrial fission.

Autor: Mei X; Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, China., Li Y; Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, China., Wu J; Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Department of Endocrinology and Metabolism, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021, China., Liao L; Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, China., Lu D; Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, China., Qiu P; Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, China., Yang HL; Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, China., Tang MW; Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, China., Liang XY; Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, China., Liu D; Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. Electronic address: 300306@hospital.cqmu.edu.cn.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Jul 05; Vol. 716, pp. 150002. Date of Electronic Publication: 2024 Apr 25.
DOI: 10.1016/j.bbrc.2024.150002
Abstrakt: Type 2 diabetes mellitus (T2DM) significantly impairs the functionality and number of endothelial progenitor cells (EPCs) and resident endothelial cells, critical for vascular repair and regeneration, exacerbating the risk of vascular complications. GLP-1 receptor agonists, like dulaglutide, have emerged as promising therapeutic agents due to their multifaceted effects, including the enhancement of EPC activity and protection of endothelial cells. This study investigates dulaglutide's effects on peripheral blood levels of CD34 + and CD133+ cells in a mouse model of lower limb ischemia and its protective mechanisms against high-glucose-induced damage in endothelial cells. Results demonstrated that dulaglutide significantly improves blood flow, reduces tissue damage and inflammation in ischemic limbs, and enhances glycemic control. Furthermore, dulaglutide alleviated high-glucose-induced endothelial cell damage, evident from improved tube formation, reduced reactive oxygen species accumulation, and restored endothelial junction integrity. Mechanistically, dulaglutide mitigated mitochondrial fission in endothelial cells under high-glucose conditions, partly through maintaining SIRT1 expression, which is crucial for mitochondrial dynamics. This study reveals the potential of dulaglutide as a therapeutic option for vascular complications in T2DM patients, highlighting its role in improving endothelial function and mitochondrial integrity.
Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare that are relevant to the content of this article. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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