血管内皮通透性增加是糖尿病血管病变的早期表现之一。研究表明胰高血糖素样肽-1(GLP-1)保护血管内皮舒张功能，但对糖尿病大血管内皮屏障功能的作用及机制仍不清楚。我们近期发现GLP-1显著缓解糖基化终末产物(AGEs)诱导的内皮细胞骨架重排，又证实具有膜骨架衔接作用的膜突蛋白(moesin)功能改变可影响血管内皮钙粘蛋白转位并减轻糖尿病血管内皮屏障功能损伤，而GLP-1能否调节moesin蛋白功能进而影响由moesin介导的糖尿病血管内皮通透性变化尚不清楚。本项目首先分析moesin蛋白在AGEs诱导血管内皮细胞屏障功能变化中的作用，继而激动或抑制相关信号通路,明确GLP-1对AGEs诱导血管内皮细胞moesin蛋白磷酸化和内皮通透性变化的影响及机制，并在糖尿病大鼠模型中证明GLP-1对动脉内皮屏障功能的作用。项目的开展为GLP-1防治糖尿病大血管内皮通透性增加提供依据。

Enhanced endothelial permeability is one of the early features of diabetic vascular disease. Glucagon-like peptide-1 (GLP-1) has been reported to protect endothelium-dependent vasodilatation. However, the effect of GLP-1 on diabetic macrovascular endothelial barrier function is still not clear. Our recent study indicated that glucagon-like peptide-1 (GLP-1) could contribute to the attenuation of skeleton rearrangement in endothelial cells incubated with advanced glycation end products (AGEs). We also found that targeted regulation of moesin could influence VE-cadherin translocation and attenuate endothelial barrier dysfunction.However,whether GLP-1 could affect the moesin, which subsequently.affect the vascular endothelial permeability mediated by moesin in diabetes is still not well defined. In this project, we firstly aim to investigate the roles of moesin in AGE induced changes of endothelial barrier function. Furthermore, we identify the effects of GLP-1 on moesin phosphorylation and endothelial permeability in endothelial cells incubated with AGEs by up-regulating or inhibiting related signal pathways. Meanwhile, the effects of GLP-1 on the arterial endothelial barrier function were also evaluated in diabetic rat model. Our study contributes to the illustration of roles of GLP-1 in preventing the increased diabetic macrovascular endothelial permeability.