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Dulaglutide restores endothelial progenitor cell levels in diabetic mice and mitigates high glucose-induced endothelial injury through SIRT1-mediated mitochondrial fission.
Mei, Xi; Li, Yao; Wu, Jinlin; Liao, Lumiu; Lu, Di; Qiu, Ping; Yang, Hui-Lan; Tang, Ming-Wei; Liang, Xin-Ying; Liu, Dongfang.
Afiliación
  • 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.
Biochem Biophys Res Commun ; 716: 150002, 2024 Jul 05.
Article en En | MEDLINE | ID: mdl-38697011
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas Recombinantes de Fusión / Fragmentos Fc de Inmunoglobulinas / Diabetes Mellitus Experimental / Péptidos Similares al Glucagón / Sirtuina 1 / Dinámicas Mitocondriales / Células Progenitoras Endoteliales / Glucosa Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas Recombinantes de Fusión / Fragmentos Fc de Inmunoglobulinas / Diabetes Mellitus Experimental / Péptidos Similares al Glucagón / Sirtuina 1 / Dinámicas Mitocondriales / Células Progenitoras Endoteliales / Glucosa Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: China