RNA Binding Proteins and Beta-cell Function

RNA 结合蛋白和 β 细胞功能

• 批准号: 6741671
• 负责人: Bentley Cheatham
• 金额: $ 24.26万
• 依托单位: RIBONOMICS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6741671
• 关键词: RNA binding protein; RNA interference; functional /structural genomics; gene expression; gene induction /repression; high throughput technology; hormone biosynthesis; hormone regulation /control mechanism; insulin; laboratory rat; messenger RNA; pancreatic islets; technology /technique development

DESCRIPTION (provided by applicant): The primary role of insulin is glucose homeostasis. The beta-cells of the endocrine pancreatic islets function to synthesize, store and secrete insulin. Elevated plasma glucose stimulates the beta-cell to acutely deploy preformed insulin-containing secretory granules that rapidly undergo regulated exocytosis, releasing insulin into the periphery. In order to restore the depleted intracellular stores of insulin, glucose also stimulates the biosynthesis of pro-insulin, processing enzymes, and a number of other unidentified cytosolic and secretory granule-associated proteins. Complex metabolic pathways that have been uniquely adapted to the beta-cell tightly regulate each of these steps. The beta-cells play a pivotal role in the pathophysiology of both Type 1 and Type 2 diabetes. During the past few years, dramatic improvements have been made in techniques for the global evaluation of cellular gene expression such as differential display and microarray analyses. Unfortunately however, such techniques often result in the production of highly complex data sets that must be organized through the use of computer models to group expressed genes into a comprehensible pattern. Therefore, a primary organizational scheme would be of great value to parse the data into functionally relevant groupings. The cell itself actually provides such an organizational structure. All mRNAs copied from all genes are processed through a series of steps to modify, splice, transport, degrade, stabilize, store, or translate the mRNAs. The experiments described in this application utilize Ribonomics' novel technology to rapidly isolate unique subsets of mRNAs that are clustered in functionally related pathways. As we will describe, this technology will allow us to; 1) better define the current understanding of signaling and metabolic pathways in the beta-cell; and 2) allow us to identify previously unknown components involved in beta-cell-specific functions. These efforts will produce a list of candidate therapeutic targets for the treatment of diabetes.

描述（由申请人提供）：胰岛素的主要作用是葡萄糖稳态。内分泌胰岛的β细胞功能可合成，存储和分泌胰岛素。升高的血浆葡萄糖刺激β细胞急性部署预先形成的胰岛素分泌颗粒，这些颗粒迅速受到调节的胞吐作用，将胰岛素释放到外围。为了恢复胰岛素的细胞内储存，葡萄糖还刺激促胰岛素，加工酶以及许多其他未鉴定的细胞质和分泌颗粒相关蛋白的生物合成。唯一适应β细胞的复杂代谢途径严格调节了这些步骤。 β细胞在类型1和2型糖尿病的病理生理学中起关键作用。在过去的几年中，在全球评估细胞基因表达（例如差异显示和微阵列分析）的全球评估技术中已进行了巨大改进。但是，不幸的是，这种技术通常会导致产生高度复杂的数据集，这些数据集必须通过使用计算机模型将基因分组为可理解的模式来组织。因此，将数据分析为功能相关的组将具有很大的价值。细胞本身实际上提供了这样的组织结构。从所有基因复制的所有mRNA都通过一系列步骤处理，以修改，剪接，运输，降解，稳定，存储或翻译mRNA。本应用程序中描述的实验利用Ribonomics的新技术来迅速分离出在功能相关途径中的mRNA的独特子集。正如我们将要描述的，这项技术将使我们能够； 1）更好地定义了β细胞中对信号传导和代谢途径的当前理解； 2）允许我们识别涉及Beta细胞特异性功能的先前未知组件。这些努力将产生用于治疗糖尿病的候选治疗靶标。