BETA CELL METABOLISM

β细胞代谢

• 批准号: 7956950
• 负责人: CHRISTOPHER B NEWGARD
• 金额: $ 1.78万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956950
• 关键词: Academic Medical Centers; Animals; Area; Arts; Beta Cell; Biochemical; Biology; Cell model; Cell physiology; Cells; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Development; Diabetes Mellitus; Disease; Functional disorder; Funding; Genes; Genetic Engineering; Glucose; Goals; Grant; Growth; Institution; Islet Cell; Islets of Langerhans; Laboratories; Life; Mass Spectrum Analysis; Measurement; Medical center; Metabolic; Metabolism; Molecular; Non-Insulin-Dependent Diabetes Mellitus; Nuclear Magnetic Resonance; Pathway interactions; Performance; Positron-Emission Tomography; Program Research Project Grants; Research; Research Personnel; Resources; Role; Source; Technology; Texas; United States National Institutes of Health; Universities; base; gene discovery; homeodomain; in vivo; insulin secretion; interdisciplinary approach; islet; metabolomics; molecular imaging; new technology; novel; programs; transcription factor

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它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，包括开发新型细胞模型、基因发现和基因工程。 该计划项目拨款 (PPG) 的首要目标仍然是开发 2 型糖尿病的新疗法。该项目从 1999 年诞生时达拉斯德克萨斯大学西南医学中心 (UTSWMC) 三个研究中心之间的合作发展到现在的形式，涉及 UTSWMC 四个中心和杜克大学医学中心的合作。该计划将继续其独特的形式，将糖尿病机制项目与专注于开发研究和治疗该疾病的新技术的项目相融合。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，我们选择将该应用程序的竞争性更新重点放在开发新策略上，以了解和逆转 2 型糖尿病的 β 细胞功能障碍。项目 1 (Newgard) 将研究先前资助期间出现的控制 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）致力于开发新型 PET 和 MR 试剂，用于体内胰岛 β 细胞的分子成像。项目 3 (Kodadek) 将创建细胞可渗透的合成分子，能够激活胰岛 β 细胞中特定性能或生长增强基因的表达。这些项目将得到管理核心（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，前者部署两种新技术，用于将分子货物递送至活体动物的胰岛 β 细胞，后者提供最先进的基于质谱 (MS) 和核磁共振 (NMR) 的技术，用于全面的代谢分析和代谢测量 通量。