Department of Endocrinology, Affiliated Hospital of Hebei University of Engineering, Handan, Hebei Province, People's Republic of China.
Department of Urology, Affiliated Hospital of Hebei University of Engineering, Handan, Hebei Province, People's Republic of China.
J Biochem Mol Toxicol. 2023 Nov;37(11):e23452. doi: 10.1002/jbt.23452. Epub 2023 Jul 7.
Diabetes mellitus (DM), becomes a main public health issue worldwide due to the rapid increase in DM patient numbers. The dysfunction of endothelial progenitor cells (EPCs) in DM patients plays a critical role in endothelial repair and the progression of DM-related vascular complications. Loxenatide is an a glucagon-like peptide 1 receptor agonist, which is used to control glycemic in type 2 diabetes patients. However, the role of Loxenatide in EPCs remains to be investigated. EPCs were isolated, characterized, and treated with Loxenatide, high-glucose, or 3-TYP. quantitative real-time polymerase chain reaction, flow cytometry, western blot, and cell counting kit-8 assay were employed to validate the expression of gene and protein expressions and cell viability, respectively. Application of Seahorse XFp to measure oxygen consumption and mitochondrial membrane potential (MMP) were measured by Seahorse XFp and MMP assay. Loxenatide attenuated high-glucose-induced reactive oxygen species (ROS) production and mitochondrial-dependent apoptosis of EPCs in a concentration-dependent manner. The EPC mitochondrial respiration dysfunction induced by high glucose was also repressed by the loxenatide treatment. The protection effect of Loxenatide on EPCs against high-glucose was applied by activating the sirtuin 3 (SIRT3)/Foxo3 signaling pathway. We demonstrated the regulatory role of Loxenatide in mitochondrial dysfunction and apoptosis of EPCs. We elucidated that Loxenatide protects EPC from high-glucose-induced apoptosis via ROS-mediated mitochondrial pathway through the SIRT3/Foxo3 signing pathway. This may provide a new therapeutical target for the treatment of DM-related vascular complications.
糖尿病（DM），由于 DM 患者数量的快速增加，成为全球主要的公共卫生问题。DM 患者内皮祖细胞（EPCs）的功能障碍在血管内皮修复和 DM 相关血管并发症的进展中起着关键作用。Loxenatide 是一种胰高血糖素样肽 1 受体激动剂，用于控制 2 型糖尿病患者的血糖。然而，Loxenatide 在 EPCs 中的作用仍有待研究。分离、鉴定 EPCs，并用 Loxenatide、高葡萄糖或 3-TYP 处理。定量实时聚合酶链反应、流式细胞术、western blot 和细胞计数试剂盒-8 测定分别用于验证基因和蛋白表达以及细胞活力的表达。应用 Seahorse XFp 测量耗氧量和线粒体膜电位（MMP），通过 Seahorse XFp 和 MMP 测定测量。Loxenatide 以浓度依赖的方式减弱了高葡萄糖诱导的 EPCs 活性氧（ROS）产生和线粒体依赖性凋亡。高葡萄糖诱导的 EPC 线粒体呼吸功能障碍也被 Loxenatide 治疗所抑制。通过激活沉默调节蛋白 3（SIRT3）/Foxo3 信号通路，Loxenatide 对 EPCs 发挥了保护作用。我们证明了 Loxenatide 对 EPCs 线粒体功能障碍和凋亡的调节作用。我们阐明了 Loxenatide 通过 ROS 介导的线粒体途径通过 SIRT3/Foxo3 信号通路保护 EPC 免受高葡萄糖诱导的凋亡。这可能为治疗 DM 相关血管并发症提供新的治疗靶点。
