Department of Internal Medicine, Hallym University College of Medicine, 896 Pyungchon-dong, Kyonggi-do, Republic of Korea.
Int J Mol Med. 2010 Dec;26(6):813-8.
Activation of the receptor for advanced glycation endproducts (RAGE) by its ligands leads to cellular damage contributing to diabetic complications. It is not clearly known whether RAGE ligands influence pancreatic β-cells. In this study, we investigated the expression of RAGE in islet cells and the effect of RAGE ligands, S100b and HMG-1, on islet cells. RAGE was expressed in INS-1 cells and isolated rat and human islets at mRNA and protein levels. RAGE and its ligand, S100b, were detected on islet cells in 28-week-old diabetic OLETF rats. Both S100b and HMG-1 induced apoptotic cell death of INS-1 and islet cells. This INS-1 cell apoptosis was accompanied by increased intracellular oxidative stress and inhibited by antioxidants or a NADPH oxidase inhibitor. Our results showing S100b/RAGE expression on islets of diabetic rat model and RAGE ligands-induced islet cell apoptosis via NADPH oxidase-mediated ROS generation suggest that RAGE ligands-RAGE interaction may contribute not only to the development of diabetic complications but also to the progressive β-cell loss in type 2 diabetes by inducing oxidative stress.
晚期糖基化终产物受体（RAGE）与其配体的激活导致细胞损伤，从而导致糖尿病并发症。目前尚不清楚 RAGE 配体是否会影响胰岛β细胞。在这项研究中，我们研究了 RAGE 在胰岛细胞中的表达以及 RAGE 配体 S100b 和 HMG-1 对胰岛细胞的影响。RAGE 在 INS-1 细胞以及分离的大鼠和人胰岛中均在 mRNA 和蛋白水平上表达。在 28 周龄的糖尿病 OLETF 大鼠的胰岛细胞上检测到 RAGE 及其配体 S100b。S100b 和 HMG-1 均可诱导 INS-1 和胰岛细胞的凋亡性细胞死亡。这种 INS-1 细胞凋亡伴随着细胞内氧化应激的增加，并且可以通过抗氧化剂或 NADPH 氧化酶抑制剂来抑制。我们的研究结果显示，在糖尿病大鼠模型的胰岛上表达 S100b/RAGE，以及 RAGE 配体通过 NADPH 氧化酶介导的 ROS 生成诱导胰岛细胞凋亡，表明 RAGE 配体-RAGE 相互作用不仅可能导致糖尿病并发症的发展，还可能通过诱导氧化应激导致 2 型糖尿病中β细胞的进行性丧失。
