胰岛β细胞功能障碍是2型糖尿病发生发展的核心环节，糖毒性是造成β细胞损伤的重要机制。转录因子MafA的表达下降介导了糖毒性作用，但慢性高糖通过何种机制抑制MafA的表达目前仍不清楚。本课题前期研究显示，硬酯酰辅酶A去饱和酶1（SCD1）正向调控MafA的表达；慢性高糖刺激抑制SCD1的表达；过表达SCD1逆转慢性高糖刺激引起的MafA表达下降。SCD1可与MafA特异性结合并抑制MafA的泛素化降解。db/db小鼠胰岛中SCD1的表达降低；β细胞干扰SCD1显著抑制胰岛素的合成和分泌。由此，我们推测，SCD1是维持β细胞功能的重要分子，其表达下降可能介导糖毒性引起的MafA表达下降。该项目旨在细胞和动物水平上，在高糖等2型糖尿病环境中，研究SCD1对胰岛β细胞功能的影响及其作用机制。本项目的完成将有助于阐明2型糖尿病糖毒性的新机制，并可能为2型糖尿病的防治提供新的潜在的作用靶点。

The failure of pancreatic β cells plays a key role in the development and outcome of type 2 diabetes. Chronic hyperglycemia, commonly called “glucotoxicity”, is a major determinant of causing β-cell failure. The downregulation of MafA expression links glucotoxicity to pancreatic β-cell dysfunction. However, the molecular mechanism of high glucoe regulating MafA expression in pancreatic β cells is unclear. Our preliminary results showed that stearoyl-CoA desaturase 1 (SCD1) positively regulated MafA expression. High gluocse treatment resulted in a decrease of SCD1 expression in β cells. SCD1 overexpression reversed the decrease of MafA expression in β cells treated with high gluocse. Further studies showed that SCD1 directly interactd with MafA and protected MafA against ubiquitylation and degradation. SCD1 mRNA and protein level was significantly decreased in islets from db/db mice compared to control mice. In β cells, interference of SCD1 impaired insulin synthesis and secretion. As a result, we speculated that SCD1 played an important role in β cell function. Downregulation of SCD1 expression contributed to the decrease of SCD1 in β cells treated with high glucose. In this study, we aim to demonstrate the role and mechanism of SCD1 in pancreatic β-cell function in type 2 diabetes using a series of in vivo and in vitro technology. And we will further explore the novel mechanism of pancreatic β-cell glucotoxicity, trying to provide a potential target for the treatment of type 2 diabetes in the future.