胰岛β细胞功能损伤是糖尿病发生发展的重要因素。目前线粒体氧化应激被认为是胰岛β细胞功能损伤的重要危险因素，但具体机制不明。Cyclophilin D（CypD）是调控线粒体氧化应激的关键蛋白，CypD介导的线粒体功能障碍是否与糖尿病的胰岛β细胞功能改变有关，国内外尚未见报道。我们前期研究发现CypD缺乏可以明显改善糖尿病小鼠的血糖和胰岛功能。另外，大量研究显示多数炎症反应可以导致线粒体功能异常，NF-κB是炎症反应中重要的转录因子，我们的前期研究发现NF-κB可以调控CypD的转录和蛋白表达。因此，本项目拟以糖尿病小鼠为研究对象，围绕线粒体关键蛋白CypD，采用体内（条件性胰岛β细胞CypD特敲小鼠）和体外（关键分子的腺病毒过表达或干扰等）相结合的技术手段，阐明NF-κB /CypD介导的线粒体应激信号通路参与糖尿病小鼠胰岛功能损伤的作用及机制，为糖尿病的治疗提供新的思路和潜在的干预靶点。

Islet beta cell function damage is an important factor in the development of diabetes. At present, mitochondrial oxidative stress is considered to be an important risk factor for islet β cell function damage, but the specific mechanism is unknown. Cyclophilin D (CypD) is a key protein regulating mitochondrial oxidative stress. Whether CypD-mediated mitochondrial dysfunction is associated with changes in islet β-cell function in diabetes has not been reported at home and abroad. Our previous study found that CypD deficiency can significantly improve blood glucose and islet function in diabetic mice. In addition, a large number of studies have shown that most inflammatory reactions can lead to mitochondrial dysfunction, NF-κB is an important transcription factor in the inflammatory response, and our previous studies found that NF-κB can regulate the transcription and protein expression of CypD. Therefore, this project intends to use diabetic mice as a research object, and focuses on the mitochondrial key protein CypD, which is combined with in vivo (conditional islet β cell CypD knockout mouse) and in vitro (key molecule overexpression or interference). The technical means to elucidate the role and mechanism of NF-κB/CypD-mediated mitochondrial stress signaling pathway in islet function damage in diabetic mice, and provide new ideas and potential intervention targets for the treatment of diabetes.