A novel, beta cell specific regulator of the insulin promoter

描述（由申请人提供）：胰腺细胞是人体唯一的胰岛素来源。β细胞的衰竭或破坏分别导致2型和1型糖尿病。我们用全基因组RNA干扰筛选鉴定了胰腺β细胞中胰岛素表达的一种新的调节因子。有趣的是，与非胰岛组织相比，这种基因似乎在β细胞中高度富集，使其成为一个有吸引力的候选者。第一个目标

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.