五羟色胺2C受体（5-HT2CR）激动剂在饮食调控和2型糖尿病发病过程中起到重要作用，5-HT2CR激动剂可激活下丘脑的5-HT2CR，改善2型糖尿病鼠的糖耐量和高胰岛素血症。而我们体外研究发现5-HT2CR激动剂能够抑制胰岛和Min-6细胞的GSIS功能，导致β细胞功能障碍——这表明5-HT2CR激动剂作用于中枢和β细胞的5-HT2CR所引起的作用是不同的。那么在动物水平5-HT2CR激动剂是否能影响β细胞分泌功能，进而影响2型糖尿病的发生发展。本项目拟借助于DIO、db/db和β细胞特异性表达5-HT2CR小鼠，研究5-HT2CR激动剂对β细胞功能的影响；并利用高通量测序和生物信息学的方法，探究其可能的机制。本项目的完成将为5-HT2CR激动剂作为药物的临床应用，特别是针对2型糖尿病患者的临床应用提供指导；也为进一步筛选更为合适的减肥药物靶点奠定基础。

Previous studies found that serotonin 2C receptor (5-HT2CR) agonists in the central nervous system played an important role in the regulation of the diet and the development of type 2 diabetes. A research had found that 5-HT2CR agonist could improve glucose tolerance and hyperinsulinism of type 2 diabetes through 5-HT2CR on hypothalamus. But our previous research had found that a 5-HT2CR agonist could inhibit glucose stimulated insulin secretion (GSIS) of beta cell, leading the dysfunction of insulin secretion in β cells. These studies showed that it is a protective effect on type 2 diabetes that 5-HT2CR agonist act on 5-HT2CR of hypothalamus, but an injury effect that 5-HT2CR agonist act on 5-HT2CR of beta cells. Then whether 5-HT2CR agonists have an effect on function of beta cells and development of diabetes and its related mechanisms in vivo, it is worthy of our further study. In this study, we plan to find the effect of 5-HT2CR agonist on the function of pancreatic β cells through DIO mice, db/db mice and the mice with pancreatic β-cell-specific expression of 5-HT2CR and its possible mechanism through high-throughput sequencing technology and bioinformatics.Our research will provide some guidances for clinical application of 5-HT2CR agonists as a medicine,especially for type 2 diabetes. It also lays the foundation for further screening of more suitable weight-loss drug targets.