BETA CELL METABOLISM

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 2009年6月10日 Newgard实验室采用跨学科方法研究葡萄糖刺激胰岛素分泌的生化和分子机制，包括开发新的细胞模型，基因发现和基因工程。 该计划项目资助（PPG）的总体目标仍然是开发2型糖尿病的新疗法。该计划已经从1999年的起源演变为达拉斯德克萨斯大学西南医学中心（UTSWMC）内的三个研究中心之间的合作，到目前的形式，涉及位于UTSWMC和杜克大学医学中心的四个中心的合作。该计划将继续以其独特的形式将糖尿病机制项目与专注于研究和治疗疾病的新技术开发的项目融合在一起。在过去的资助周期中，最引人注目的进展发生在胰岛生物学和相关技术领域。因此，我们选择将该申请的竞争性更新集中在开发用于理解和逆转2型糖尿病β细胞功能障碍的新策略上。项目1（Newgard）将研究在前一资助期出现的控制β细胞功能和生长的新途径，特别是同源域转录因子Nkx6.1在正常和功能失调的成熟胰岛细胞生物学中的作用。项目2（Sherry）旨在开发用于体内胰岛β细胞分子成像的新型PET和MR试剂。项目3（Kodadek）将创建能够激活胰岛β细胞中特定性能或生长增强基因表达的细胞渗透性合成分子。这些项目将得到行政核心（核心A）、胰岛靶向核心（核心B）和代谢组学核心（核心C）的支持，胰岛靶向核心部署了两种新技术，用于将分子货物输送到活体动物的胰岛β细胞，代谢组学核心提供了最先进的质谱（MS）和核磁共振（NMR）技术，用于全面的代谢分析和代谢通量测量。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. June-10-2009 The Newgard laboratory uses interdisciplinary approaches for the study of the biochemical and molecular mechanisms involved in glucose-stimulated insulin secretion, including development of novel cellular models, gene discovery and genetic engineering. The overarching goal of this program project grant (PPG) continues to be the development of novel therapies for type 2 diabetes. The program has evolved from its genesis in 1999 as a collaboration between three research Centers within the University of Texas Southwestern Medical Center in Dallas (UTSWMC) to its current format, involving collaboration of four Centers located at UTSWMC and Duke University Medical Center. The program will continue with its unique format of melding projects on diabetes mechanisms with projects focused on development of new technologies for studying and treating the disease. In the past funding cycle, the most compelling advances have occurred in the area of pancreatic islet biology and related technologies. We have therefore chosen to focus the competitive renewal of this application on development of new strategies for understanding and reversing beta-cell dysfunction of type 2 diabetes. Project 1 (Newgard) will investigate novel pathways for control of beta-cell function and growth that have emerged in the prior funding period, particularly the role of the homeodomain transcription factor Nkx6.1 in the biology of normal and dysfunctional mature islet cells. Project 2 (Sherry) seeks to develop novel PET and MR agents for molecular imaging of islet beta-cells in vivo. Project 3 (Kodadek) will create cell permeable synthetic molecules capable of activating the expression of specific performance- or growth-enhancing genes in islet beta-cells. These projects will be supported by an Administrative Core (Core A), an Islet Targeting Core (Core B), which deploys two novel technologies for delivery of molecular cargo to islet beta-cells in living animals, and a Metabolomics Core (Core C), which provides state-of-the-art mass spectrometry (MS)- and nuclear magnetic resonance (NMR)-based technologies for comprehensive metabolic profiling and measurement of metabolic flux.