Reg3b调控胰岛β细胞再生的作用及其机制

We find that Reg3b is highly expressed in the β cell of pancreatic compensatory proliferation mouse model that we have set up by continuous intravenous high concentration of glucose infusion. The same result has been confirmed by real-time quantitative PCR experiments, and we also confirmed the Reg3b can contribute to the proliferation of islet cell strains Min6 in vitro experiments. we are ready to take advantage of the sustained high glucose infusion and partial pancreatic Pancreatectomy induced pancreatic β-cell compensatory proliferation mouse model to detect Reg3b and its downstream expression of proliferation-related molecules. Reg3b specific role in the regulation of pancreatic β-cell compensatory proliferation will be researched through the establishment of Reg3b high expression or low / non-active cell model, and further explore will focous on the specific mechanism. The role of reg3b in the neogenesis of islets will also be explored by the model of PDL. This subject has a certain degree of innovation, and it is of great significance for us to understand the mechanism of beta cell regeneration as well as to explore the treatment of type 2 diabetes .

本课题利用前期建立的静脉持续高浓度葡萄糖灌注诱导的胰岛β细胞代偿性增殖小鼠模型，通过基因芯片技术发现Reg3b在代偿性增殖的胰岛β细胞高表达，后经实时定量PCR实验证实。我们还通过体外细胞实验证实了Reg3b能够促进胰岛细胞株Min6的增殖。本课题准备利用持续高糖灌注和胰腺部分切除诱导的胰岛β细胞代偿性增殖小鼠模型以及葡萄糖、GLP-1等促β细胞增殖因子所致的β细胞增殖模型检测Reg3b及其调控的下游增殖相关分子的表达；并通过建立Reg3b高表达或低/无活性细胞模型，明确Reg3b在调控胰岛β细胞代偿性增殖中的具体作用，并进一步探讨其具体机制。此外我们还利用胰腺导管结扎诱导胰岛细胞新生的模型探讨Reg3b在胰岛细胞新生中的作用。本课题具有一定的创新性，对于深入了解β细胞再生机制以及探寻治疗2型糖尿病的靶点，具有重要意义。

我们通过前期建立的建立的持续灌注高浓度葡萄糖和胰腺部分切除诱导的胰岛β细胞代偿性增殖小鼠模型证实了reg3b在胰岛β细胞代偿性增殖中的作用，并初步探讨了其机制。此外我们还发现60%胰腺部分切除能够激活胰岛β细胞的mTOR信号，通过rapamycin的抑制试验证实了mTOR信号参与了60%胰腺部分切除能够激活胰岛β细胞的代偿性增殖。我们进一步给胰岛β细胞特异性敲除Rictor小鼠进行60%胰腺部分切除试验，其胰岛β细胞的代偿性增殖并未发生明显改变，结合的rapamycin抑制试验我们推断60%胰腺部分切除诱导胰岛β细胞的代偿性增殖主要通过mTORC1介导而非通过mTORC2。本研究明确了reg3b和 mTOR信号在胰岛β细胞代偿性增殖中的作用，并探讨了其机制。本研究对于深入了解胰岛β细胞的的增殖机制以及2型糖尿病药物靶点的研究具有一定的潜在意义。