从胰岛素瘤等组织筛选调节胰岛素分泌及基因表达的基因

Insulinoma is a common cause of organic hypoglycemia clinically.The prominent characteristics of insulinoma are endogenous hyperinsulinism and continuous secretion of insulin uncontrolled by glycemia.Until now,the pathogenesis of human insulinoma remains unclear.In the present study,the gene expression profiling of human insulinoma tissue was firstly established by ESTs sequencing and cDNA microarray,which illuminated the biological behaviour at gene level.Compared with human normal pancreatic tissue,the genes invovled in tumorigenesis,signal transduction pathway and secretion of insulin were augmented obviously in human insulinoma tissue.These highly-expressed genes provided us a platform through which the pathogenesis of insulinoma and automatic insulin secretion were studied.After further research had been conducted, we found that Gsα is the most likely cause of proliferation and tumorigenesis of pancreatic islet beta cells.We also found that increased expression of genes pertain to insulin secretion,such as PDIA3、SSR2、GOS-28、AP4 and CPE, positively fedback insulin biosynthesis,which accounted for continuous hypersecretion of insulin.In addition,five new full-length cDNA were cloned among known ESTs by method of in silico cloning.Predicted by protein functional domain and signal peptide prediction softwares,a new Na+/Ca2+ exchanger protein which maybe play an important role in regulating Ca2+ of islet beta cells and insulin secretion was found.In addition,two new genes had signal peptides which were implicated as new secretory proteins in pancreatic islet beta cells or insulinoma tissue.

胰岛素瘤是研究、克隆胰岛素基因表达和胰岛素分泌的极佳模型。本课题组已构建胰岛素瘤cDNA文库并从垂体组织中克隆到GLP、G-144及HSGⅢ。本课题旨在从胰岛素瘤组织中筛选和寺〉鹘谝鹊核鼗虮泶锛耙鹊核胤置诘幕蛞约凹煅镚LP、G-144及HSGⅢ对胰岛素分泌的影响。此研究对糖尿病发病机制的研究及开发治疗糖尿病新药具有重要意义。