胰源性糖尿病（T3cDM）主要发病原因是慢性胰腺炎（CP），其胰腺癌发生风险显著增加，但机制不明。CP主要病理特征是胰腺纤维化，胰腺星状细胞（PSC）活化是其关键环节，可能参与T3cDM发生。最新研究表明，CP 过程中胰多肽（PP）缺乏、GLP-1受损、胰岛素减少、胰高糖素相对增多，促进了 T3cDM 发生发展。我们前期研究发现，CP 时胰腺应激蛋白PSP/reg 显著增高，抑制PSC活化，而PSP/reg是胰岛β细胞再生因子，PSP/reg是否通过抑制PSC活化而减轻胰岛纤维化，发挥胰腺自身保护作用，值得进一步探讨。本课题拟建立CP相关性T3cDM大鼠模型，观察CP过程中胰腺炎部位、PSC活化及胰岛纤维化程度，检测PP、GLP-1、胰岛素、胰高血糖素及PSP/reg水平，基因芯片分析T3cDM大鼠基因表达谱的变化，探寻胰腺外分泌功能变化与内分泌之间的联系，为临床防治T3cDM提供新思路。

The eventual course of pancreatogenic diabetes (T3cDM) is impacted by a high risk for the development of pancreatic cancer in the majority of patients whose diabetes is a consequence of chronic pancreatitis (CP). The key histopathologic feature of CP is pancreatic fibrosis. Pancreatic stellate cells (PSCs) are now established as key cells in fibrogenesis. Recent studies show that T3cDM develops in the setting of insulin deficiency, pancreatic polypeptide (PP) deficiency and impaired glucagon-like peptide 1(GLP-1) secretion during the course of CP. Our previous study suggested that increased pancreatic stress protein /regenerating protein (PSP/reg) in the repair phase of chronic pancreatitis inhibited PSC activation. While PSP/reg is mitogenic to islet βcells, our data show that PSP/reg inhibited the proliferation of PSCs endorse our view that PSP/reg may have a protective function during the reorganization of the injured pancreas. This is interesting and require for further investigation. Our current study is to establish animal models of T3cDM secondary to CP, evaluate pancreas histology and PSCs activation, determine blood biochemical values including fasting blood glucose, insulin, glucagon, PP and GLP-1, investigate the changes of genome expression profiles, in order to explore the relationship between the exocrine and endocrine of the pancreas and provide new insight into T3cDM.