成体β细胞的成熟分化状态是功能性β细胞容量重要组成部分，它的异常会导致糖尿病的发生。课题组已发表的研究证实，mTORC1在β细胞功能，凋亡及增殖中都起到重要的作用。课题组在β细胞选择性敲除mTORC1伴随蛋白Raptor的小鼠 (ßRapKO)中观察到β细胞的不成熟表型，及转分化现象，同时伴有甲基化转移酶DNMT3a表达下调和部分成熟相关基因甲基化的改变。本研究提出 “mTORC1 通过甲基化调控胰岛β细胞成熟分化”的假说，将使用创新的“β细胞EGFP特异表达的Raptor敲除小鼠”，在活体示踪下高效精准地观察mTORC1对β细胞成熟分化的影响，在GFP+β细胞上展开基因芯片和甲基化高通量测序，生物信息联合分析找到甲基化调控的关键因子，并在INS1细胞上深入探讨DNMT3a参与成熟分化的潜在机制。相信mTORC1/甲基化参与β细胞的成熟分化的机制研究，将为治疗糖尿病提供理论基础和研发思路。

Normal beta cell maturation and differentiation state is an essential component of functional beta cell mass, and its defect will lead to onset of diabetes. Our published results have confirmed that mTORC1 plays an important role in beta cell function, apoptosis and proliferation. Interestingly, using our newly estabolished transgenic model, beta cell specific raptor knockout mice (ßRapKO), we observed immature beta cell phenotye, beta cell trans-differentiation and downregulation of DNA methyltransferases DNMT3a after mTORC1 ablation. Based on these observations, we hypothesized that “mTORC1 regulates pancreatic beta cell maturation and differentiation via DNA methylation”. The present study will use novel in vivo tracing system “β Cell specific EGFP expression Raptor knockout mice（ßRaptorKOGFP）”to clarify the effect of mTORC1 in different stages of beta cell maturation, perform microarray and Medip seq on puried GFP+ ß cells to identify core factors that are regulated by mTORC1-dependent DNA methylation, and carry out DNMT3a mechanism experiments in INS1 cells. We believe our study will provide a novel insight of treatment of diabetes.