Guo Zi
Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06510, USA.
Pharmacol Rep. 2024 Aug;76(4):754-779. doi: 10.1007/s43440-024-00609-1. Epub 2024 Jun 19.
Diabetes leads to a significantly accelerated incidence of various related macrovascular complications, including peripheral vascular disease and cardiovascular disease (the most common cause of mortality in diabetes), as well as microvascular complications such as kidney disease and retinopathy. Endothelial dysfunction is the main pathogenic event of diabetes-related vascular disease at the earliest stage of vascular injury. Understanding the molecular processes involved in the development of diabetes and its debilitating vascular complications might bring up more effective and specific clinical therapies. Long-acting glucagon-like peptide (GLP)-1 analogs are currently available in treating diabetes with widely established safety and extensively evaluated efficacy. In recent years, autophagy, as a critical lysosome-dependent self-degradative process to maintain homeostasis, has been shown to be involved in the vascular endothelium damage in diabetes. In this review, the GLP-1/GLP-1R system implicated in diabetic endothelial dysfunction and related autophagy mechanism underlying the pathogenesis of diabetic vascular complications are briefly presented. This review also highlights a possible crosstalk between autophagy and the GLP-1/GLP-1R axis in the treatment of diabetic angiopathy.
糖尿病会导致各种相关大血管并发症的发病率显著加速上升,包括外周血管疾病和心血管疾病(糖尿病患者最常见的死亡原因),以及诸如肾病和视网膜病变等微血管并发症。内皮功能障碍是糖尿病相关血管疾病在血管损伤最早阶段的主要致病事件。了解糖尿病及其使人衰弱的血管并发症发生发展过程中涉及的分子过程,可能会带来更有效、更具特异性的临床治疗方法。长效胰高血糖素样肽(GLP)-1类似物目前可用于治疗糖尿病,其安全性已得到广泛确立,疗效也经过了广泛评估。近年来,自噬作为一种维持体内平衡的关键的、依赖溶酶体的自我降解过程,已被证明与糖尿病中的血管内皮损伤有关。在本综述中,简要介绍了与糖尿病性内皮功能障碍相关的GLP-1/GLP-1R系统以及糖尿病血管并发症发病机制背后的相关自噬机制。本综述还强调了自噬与GLP-1/GLP-1R轴在糖尿病血管病治疗中可能存在的相互作用。