慢性低度炎症促进2型糖尿病发生发展，但具体机制不清。我们前期研究表明：1.二肽基肽酶4(DPP4)与IGF-2受体作用发挥促炎功能进而促进2型糖尿病发生2.调节性 T 细胞（Treg）表面表达IGF-2受体3.DPP4下调Treg细胞关键功能基因Foxp3表达4.DPP4抑制Treg细胞分化。既往研究还表明，Foxp3基因表达和Treg细胞功能发挥需胞内PI3K-Akt-mTOR信号通路处于抑制状态，DPP4抑制剂可下调PI3K-Akt-mTOR信号通路。据此，我们推测，DPP4可能作用Treg细胞表面IGF-2受体，激活胞内PI3K/Akt/mTOR通路，下调Foxp3基因表达，抑制Treg细胞抗炎功能。本课题采用RCT研究、T 细胞培养、流式细胞仪等方法，在活体和细胞水平，阐明DPP4酶学与非酶学特性对Treg细胞分化、增殖及抑炎功能的影响和机制，旨在改善2型糖尿病的慢性低度炎症状态。

The onset and development of type 2 diabetes are promoted by chronic low-grade inflammation, however, the underlying mechanism remains unclear. Our previous research indicated that 1. DPP4 promote the onset and development of type 2 diabetes through its interaction with IGF-2 receptor to enhance the proinflammatory state. 2. Treg cell surface express IGF-2 receptor. 3. DPP4 downregulate the expression of Foxp3 in Treg cell. 4. DPP4 inhibits the differentiation of Treg cell. Furthermore, recent studies showed that relatively low activity of the PI3K/Akt/mTOR pathway is essential for the normal expression of Foxp3 and function of Treg cell，DPP4 inhibitors downregulate the PI3K/Akt/mTOR pathway. Consequently, we speculate that DPP4 interacts with IGF-2 receptor on the surface of Treg cell and results in the upregulation of PI3K/Akt/mTOR pathway, which leads to a decrease in the expression of Foxp3. This, ultimately inhibits the anti-inflammatory function of Treg. Accordingly, in this study we will perform mainly randomized controlled trial, ex vivo T cell culture, followed by flow cytometry (FACS),etc, to prove the enzymatic and nonenzymatic inhibitory effects of DPP4 exerted on the differentiation, proliferation and anti-inflammatory function of Treg and its related mechanism. This research is crucial for prevention and treatment of type 2 diabetes by attenuating the proinflammatory state in such disease.