本课题组将在胰岛β细胞特异性敲除mTORC1（βRapKO）和 mTORC2(βRicKO)小鼠上运用已建成的三种活体胰岛增殖模型"60%胰腺切除增殖模型"，"高糖灌注增殖模型"，"第15天孕鼠增殖模型"，比较mTORC1和mTORC2两个蛋白分子在生理，病理，手术等不同诱因引起的胰岛代偿增殖中的作用,及对下游不同增殖转录因子和细胞周期蛋白谱的调控。运用胰岛β细胞特异性TSC1敲除小鼠（βTSC1KO），导管Rictor腺病毒注射等"功能缺失和获得"的确证分析，探讨mTORC1-mTORC2调节环在代偿增殖中独立和联合的作用。在机制研究中，我们将使用SiRNA,免疫沉淀印记等技术深入探讨核糖体蛋白参与mTORC1-mTORC2的调节环的桥梁作用。相信本项研究结果将展示mTOR环路调节胰岛β细胞增殖的全景图，为糖尿病治疗的新药筛选提供一个有效平台。

The present study will perform three established in vivo pancreatic beta cell proliferation models, i.e."60% pancretectomy","Glucose-infusion","Pregnancy" on beta cell specific mTORC1(βRapKO) and mTORC2 (βRicKO)knock out mice, which enable us to compare the roles of mTORC1 and mTORC2 proteins on pancreatic beta cell proliferation and understand their underlying mechanisms involving transcriptional factors and cell cycle proteins. "Gain and loss function" study using pancreatic beta cell specific TSC1 knock out mice（βTSC1KO）and Rictor over-expression through adenovirus injection will help us to identify mTORC1-mTORC2 regulatory loop on beta cell adaptation and to prove the redundant and independent characteristics of the two signal pathways. We will use SiRNA, immunoprecipitation method to further discuss the possible involvement of ribosomal proteins in mTORC1-mTORC2 loop regulation. We believe our result would provide a panorama of mTORCs in pancreatic beta cell research, a novel insight of treatment of diabetes by regulating pancreatic beta cell mass and an efficient platform of screening new drugs.