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

作者全名：Mei, Xi; Li, Yao; Wu, Jinlin; Liao, Lumiu; Lu, Di; Qiu, Ping; Yang, Hui-lan; Tang, Ming-wei; Liang, Xin-ying; Liu, Dongfang

作者地址：[Mei, Xi; Wu, Jinlin; Lu, Di; Liu, Dongfang] Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol & Metab, Chongqing 400010, Peoples R China; [Mei, Xi; Li, Yao; Liao, Lumiu; Lu, Di; Qiu, Ping; Yang, Hui-lan; Tang, Ming-wei; Liang, Xin-ying] Chengdu Med Coll, Affiliated Hosp 1, Dept Endocrinol & Metab, Chengdu 610500, Sichuan, Peoples R China; [Wu, Jinlin] Chongqing Hosp Tradit Chinese Med, Dept Endocrinol & Metab, Chongqing 400021, Peoples R China

通信作者：Liu, DF (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol & Metab, Chongqing 400010, Peoples R China.

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001237883900001

JCR分区：Q3

影响因子：2.5

年份：2024

卷号：716

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Dulaglutide; T2DM; Endothelial cells; Mitochondrial dynamics; SIRT1

摘要：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 highglucose-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.

基金机构：Key discipline construction project of Sichuan Province, China; Sichuan Collaborative Innovation Center for Elderly Care and Health of Chengdu Medical College, China [YLZBZ2008]; Medical Research Youth Innovation Project of Sichuan Medical Association, China [20230205070029]

基金资助正文：<STRONG> </STRONG>This study is funded by the Key discipline construction project of Sichuan Province, China; Sichuan Collaborative Innovation Center for Elderly Care and Health of Chengdu Medical College, China (YLZBZ2008) ; Medical Research Youth Innovation Project of Sichuan Medical Association, China (20230205070029) .