胰岛功能缺陷与胰岛素抵抗(IR)为2型糖尿病发病的两个决定因素，但胰岛功能缺陷与胰岛β细胞自噬的关系尚不清楚。前期工作中，我们构建SD鼠IR动物模型，首次从IR鼠胰岛组织中鉴定出差异表达基因--增食欲素受体1（OX1R），并发现Orexin/OX1R与胰岛β细胞自噬相关。本项目将建立"高表达"或"沉默"OX1R和自噬相关基因Atg7的胰岛β细胞株，分析OX1R对胰岛β细胞分泌、自噬及PI3K-mTOR信号通路的影响，研究胰岛β细胞内OX1R/FOXO1因子的相互作用机制，观测Atg7特异性敲除小鼠胰岛内的OX1R和FOXO1功能特性，通过ChIP-on-chip技术和自噬基因芯片技术鉴定出启动OX1R与FOXO1蛋白相互作用的可能的细胞自噬因子，以期阐明在胰岛β细胞自噬中Orexin/OX1R激动FOXO1/Atg7的作用机制，可望为探索胰岛β细胞功能缺陷的治疗策略提供潜在的新靶点。

Functional defect of pancreas islet and insulin resistance are determinative factors in 2 type diabetes. The effect of autophagy on functional defect of pancreas islet is not clear. In this study, we have firstly identified the differential expression of orexin receptor 1 (OX1R) in pancreas islet in insulin-resistance rat model. The pancreas islet beta cell with high- expression or silence of OX1R and autophagy-related gene 7 (Atg7) will be cultivated. The effect of OX1R on cell secretion, autophagy, and PI3K-mTOR signal pathway in beta cell will be studied. The interaction mechanism between OX1R and FOXO1 will be Clarified. The downstream gene regulated with OX1R will be identified by cDNA array screening. The possible autophagy factors started the interaction between OX1R and FOXO1 will be try to find by autophagy gene chip technology and ChIP-on-chip technique. It will be elucidated that orexin/OX1R/FOXO1/Atg7 signal pathway, the function and mechanism of action of OX1R in autophagy in beta cell of pancreas islet, and explore the experimental treatment for function defects of islet β-cell.