Control of islet beta specific pdx-1 and mafA transcription

胰岛素在胰岛的B细胞中合成。生理葡萄糖水平通过这种激素对外周组织的作用来维持，P细胞功能的缺陷涉及糖尿病患者中高血糖的起始和维持。直到最近，人们对控制胰腺发育和胰岛P细胞功能的因素知之甚少。然而，由于对胰岛素启动子的研究，我们的理解大大增加，这导致了富含胰岛的转录因子PAX 6，PDX-1，MafA和BETA 2的鉴定和分子表征。基因敲除在 这些因素和其他胰腺富集因素有助于阐明影响胰腺癌的事件， 胰腺形态发生下一步是了解这些重要调节因子的表达和活性水平是如何控制的。在这些研究中，可能会发现P细胞功能所必需的新因素。由于它们独特的表达模式和对P细胞的重要意义，我们的目标集中在确定参与控制pdx-1和ma/A选择性表达的转录因子。此外，我们将测试p300和CBP共激活剂对P细胞的体内意义，这些共激活剂是对与b细胞身份相关的许多基因的表达至关重要的衔接分子。这些研究将提供更深入的了解基本的P细胞活性的转录成分，并可能提供的信息，将是必不可少的，在产生可接受的胰岛样细胞的治疗性治疗1型和2型糖尿病。

Insulin is synthesized in the b cells of the islets of Langerhans. Physiological glucose levels are maintained through the action of this hormone on peripheral tissues, with defects in P cell function involved in initiating and maintaining hyperglycemia in diabetics. Little detailed information was known about the factors controlling pancreas development and islet P cell function until recently. However, our understanding has increased greatly as a result of studies on the insulin promoter, which led to the identification and molecular characterization of the islet-enriched transcription factors PAX6, PDX-1, MafA and BETA2. The gene knockouts performed on these factors and other pancreas-enriched factors are helping elucidate the events influencing pancreatic morphogenesis. The next step is to understand how the expression and activity levels of these important regulators are controlled. It is likely that new factors necessary for P cell function will be revealed in these studies. Because of their unique expression pattern and fundamental significance to P cells, our objectives are focused on defining the transcription factors involved in controlling selective .expression of pdx-1 and ma/A. In addition, we will test the in vivo significance to the P cell of the p300 and CBP co-activators, adapter molecules that appear critical for expression of many genes associated with b-cell identity. These studies will provide greater insight into the transcriptional components fundamental to P cell activity, and likely provide information that will be essential in generating acceptable islet-like cells for therapeutic treatment of type 1 and type 2 diabetics.