Department of Ophthalmology, The First People's Hospital of Xianyang, No. 10, Biyuan Road, Qindu District, Xianyang City, 712000, Shanxi, China.
Department of Ophthalmology, Sanyuan Eye Hospital, Xianyang City, 713899, Shanxi, China.
Hum Cell. 2024 May;37(3):666-674. doi: 10.1007/s13577-024-01038-1. Epub 2024 Mar 4.
Diabetes mellitus (DM) is a chronic metabolic disorder affecting millions of people worldwide, characterized by dysregulated glucose homeostasis and hyperglycemia. Diabetic retinopathy (DR) is one of the serious multisystemic complications. Aging is an important risk factor for DR. Endothelial sirtuin 1 (SIRT1) plays an important role in regulating the pathophysiology of glucose metabolism, cellular senescence, and aging. Liraglutide, an analog of Glucagon-like peptide 1 (GLP-1), has been widely used in the treatment of DM. However, the effects of Liraglutide on DR are less reported. Here, we investigated whether treatment with Liraglutide has beneficial effects on high glucose (HG)-induced injury in human retinal microvascular endothelial cells (HRECs). First, we found that exposure to HG reduced the expression of glucagon-like peptide 1 receptor 1 (GLP-1R). Additionally, Liraglutide ameliorated HG-induced increase in the expression of vascular endothelial growth factor-A (VEGF-A) and interleukin 6 (IL-6). Importantly, Liraglutide ameliorated cellular senescence and increased telomerase activity in HG-challenged HRECs. Liraglutide also reduced the levels of p53 and p21. Mechanistically, Liraglutide restored the expression of SIRT1 against HG. In contrast, the knockdown of SIRT1 abolished the protective effects of Liraglutide in cellular senescence of HRECs. Our findings suggest that Liraglutide might possess a benefit on DR mediated by SIRT1.
糖尿病（DM）是一种影响全球数百万人的慢性代谢紊乱，其特征是葡萄糖稳态失调和高血糖。糖尿病视网膜病变（DR）是一种严重的多系统并发症。衰老也是 DR 的一个重要危险因素。内皮沉默调节蛋白 1（SIRT1）在调节葡萄糖代谢、细胞衰老和衰老的病理生理学方面发挥着重要作用。利拉鲁肽是胰高血糖素样肽 1（GLP-1）的类似物，已广泛用于治疗糖尿病。然而，利拉鲁肽对 DR 的影响报道较少。在这里，我们研究了利拉鲁肽是否对人视网膜微血管内皮细胞（HRECs）的高葡萄糖（HG）诱导损伤有有益作用。首先，我们发现暴露于 HG 会降低胰高血糖素样肽 1 受体 1（GLP-1R）的表达。此外，利拉鲁肽改善了 HG 诱导的血管内皮生长因子-A（VEGF-A）和白细胞介素 6（IL-6）表达增加。重要的是，利拉鲁肽改善了 HG 挑战的 HRECs 中的细胞衰老并增加了端粒酶活性。利拉鲁肽还降低了 p53 和 p21 的水平。在机制上，利拉鲁肽恢复了 SIRT1 的表达以对抗 HG。相反，SIRT1 的敲低消除了利拉鲁肽在 HRECs 细胞衰老中的保护作用。我们的研究结果表明，利拉鲁肽可能对 SIRT1 介导的 DR 具有益处。
