A novel, beta cell specific regulator of the insulin promoter

描述（由申请人提供）：胰腺β细胞是人体胰岛素的唯一来源。2型糖尿病是指2型糖尿病患者的糖尿病。我们通过全基因组RNA干扰筛选，在胰腺β细胞中发现了一种新的胰岛素表达调节因子。有趣的是，该基因似乎在β细胞与非胰岛组织中高度富集，使其成为一个有吸引力的候选者。第一个目标是 R03建议研究小鼠敲除该基因。具体而言，将在缺乏该基因的β细胞表达的小鼠中测量胰岛素表达、葡萄糖耐受性、胰岛素耐受性和胰岛素分泌。第二个目标是询问在人类胰岛中敲低该基因的人类同源物是否也影响胰岛素表达和胰岛素分泌。为此，靶向该基因的小发夹RNA将使用腺病毒递送到人类胰岛中。然后，将测量胰岛素启动子活性和葡萄糖刺激的胰岛素分泌。本申请的目的是提供关键的体内数据，以支持R01在β细胞功能中该基因的详细机制方面的应用。

DESCRIPTION (provided by applicant): The pancreatic beta cell is the body's only source of insulin. The failure or destruction of the beta cell results in type 2 and type 1 diabetes respectively. We identified a novel regulator of insulin expression in the pancreatic beta cell wit a whole genome RNA interference screen. Interestingly, this gene appears to be highly enriched in the beta cell versus non-islet tissues, making it an attractive candidate. The first aim of this R03 proposes to study the mouse knockout of this gene. Specifically, insulin expression, glucose tolerance, insulin tolerance, and insulin secretion will be measured in mice lacking beta cell expression of this gene. The second aim asks if knockdown of the human homolog of this gene in human islets also affects insulin expression and insulin secretion. To do this, small hairpin RNAs targeting this gene will be delivered into human islets using adenovirus. Then, insulin promoter activity and glucose stimulated insulin secretion will be measured. The goal of this application is to provide critical in vivo data to support an R01 application on the detailed mechanism of this gene in beta cell function.