青年基金项目发现胰腺分泌应激蛋白PSP/reg在慢性胰腺炎时显著升高，可能通过抑制胰腺星状细胞 (PSC) 活化，推动胰腺纤维化逆转，促进组织再生修复，从而发挥胰腺的自身保护作用。近年来研究表明，2型糖尿病 (T2DM) 重要环节是胰岛纤维化，PSP/reg是公认的胰岛β细胞再生因子，PSP/reg是否通过抑制胰岛PSC活化减轻胰岛纤维化从而改善胰岛β 细胞功能，值得进一步探讨。T2DM是胰腺癌发生的危险因素，高糖高胰岛素环境下PSC 活化是胰岛和胰腺纤维化发生的始动和关键环节，可能参与了T2DM与胰腺癌的发生发展。本课题拟利用基因重组的PSP/reg 和药物干预，比较胰岛形态结构、β 细胞功能、PSC活性及胰腺纤维化的演变，检测不同病程T2DM与发生胰腺癌患者血清PSP/reg 水平，探讨PSP/reg对T2DM胰岛和胰腺纤维化的影响及细胞分子机制，为治疗T2DM和防治胰腺癌提供新思路。

Our current ongoing research funded by National Natural Science Fund for Youth has found that PSP/reg was significantly increased in chronic pancreatitis. It may act through inhibiting the activation of PSC, a central player for developing pancreatic fibrosis, subsequently reverses the pancreatic fibrosis and enhances the pancreatic regeneration after injury; therefore it may play a role in pancreatic natural protective process. Recent studies suggest that islet fibrosis is the key step to the development of type 2 DM (T2DM), and it is well known PSP/reg is a growth factor for islet beta cell regeneration. Whether or not it is through inhibiting PSC activation for PSP/reg to reduce islet fibrosis and in turn improve islet beta cell function remains to be investigated. T2DM is a risk factor for the development of pancreatic carcinoma. Under the influence of hyperglycemia and hyperinsulinemia, PSC activation is the initiating and key step for developing islet and pancreatic fibrosis and may play an important role in the pathogenesis and progression of pancreatic carcinoma, while the underlying mechanisms remain to be explored. Based on our discovery from our ongoing funded project, by using PSP/reg and clinical available T2DM treatment medications, Our current application is to focus on the morphological characteristics of the islet, beta cell function, PSC activation and the genesis and resolution of fibrosis, to compare PSP/reg levels in patients with pancreatic cancer and corresponding clinical stages of T2DM; to further investigate the effect and potential molecular mechanisms of PSP/reg on islet fibrosis and pancreatic fibrosis in patient with T2DM, and eventually to provide new treatment targets for T2DM and pancreatic cancer.