Zhou Huan-Ran, Ma Xue-Fei, Lin Wen-Jian, Hao Ming, Yu Xin-Yang, Li Hong-Xue, Xu Cheng-Ye, Kuang Hong-Yu
Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Pharmacol. 2021 Feb 12;11:589114. doi: 10.3389/fphar.2020.589114. eCollection 2020.
GLP-1 analogs have been widely used to treat patients with type 2 diabetes in recent years and studies have found that GLP-1 analogs have multiple organ benefits. However, the role of GLP-1 analogs in diabetic retinopathy (DR), a common complication of diabetes mellitus (DM), remains controversial. Retinal ganglion cells (RGCs) are the only afferent neurons responsible for transmitting visual information to the visual center and are vulnerable in the early stage of DR. Protection of RGC is vital for visual function. The incretin glucagon-like peptide-1 (GLP-1), which is secreted by L-cells after food ingestion, could lower blood glucose level through stimulating the release of insulin. In the present study, we evaluated the effects of GLP-1 analog on RGCs both and . We established diabetic rat models and applied an RGC-5 cell line . The results showed that in high glucose conditions, GLP-1 analog alleviated the damage of RGCs. In addition, GLP-1 analog prevented mitophagy through the PINK1/Parkin pathway. Here we demonstrated the neuroprotective effect of GLP-1 analog, which may be beneficial for retinal function, and we further elucidated a novel mechanism in GLP-1 analog-regulated protection of the retina. These findings may expand the multi-organ benefits of GLP-1 analogs and provide new insights for the prevention of DR.
近年来,胰高血糖素样肽-1(GLP-1)类似物已被广泛用于治疗2型糖尿病患者,并且研究发现GLP-1类似物对多个器官有益。然而,GLP-1类似物在糖尿病视网膜病变(DR)(糖尿病(DM)的一种常见并发症)中的作用仍存在争议。视网膜神经节细胞(RGCs)是唯一负责将视觉信息传递到视觉中枢的传入神经元,并且在DR早期易受损伤。保护RGC对视觉功能至关重要。进食后由L细胞分泌的肠促胰岛素胰高血糖素样肽-1(GLP-1)可通过刺激胰岛素释放来降低血糖水平。在本研究中,我们评估了GLP-1类似物对RGCs的体内和体外作用。我们建立了糖尿病大鼠模型并应用了RGC-5细胞系。结果表明,在高糖条件下,GLP-1类似物减轻了RGCs的损伤。此外,GLP-1类似物通过PINK1/Parkin途径阻止了线粒体自噬。在此,我们证明了GLP-1类似物的神经保护作用,这可能对视网膜功能有益,并且我们进一步阐明了GLP-1类似物调节视网膜保护的新机制。这些发现可能扩展GLP-1类似物的多器官益处,并为DR的预防提供新的见解。