Differentiated function of tissues involved in nutrition and metabolism

参与营养和代谢的组织的分化功能

• 批准号: 7921981
• 负责人: Morris Jay Birnbaum
• 金额: $ 182.89万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7921981
• 关键词: Differentiated; function; tissues; involved; nutrition

Diabetes is increasingly recognized to be influenced by complex genetic and metabolic factors involving multiple organs and molecules. A single important molecule may directly or indirectly control the function of other molecules and multiple tissues. The function of an adult tissue is clearly dependent upon its history, i.e., its differentiation and development, as well as upon signals emanating from other tissues and the environment. This Program Project Grant involves five outstanding investigators, each focused on a specific molecule that regulates development and metabolic function of a specific tissue. Project 1 (Lazar) addresses the role of resistin, a novel adipocyte-secreted factor (adipokine), in insulin resistance and atherosclerosis. Project 2 (Ahima) examines the role of the central nervous system in mediating the metabolic effects of adipokines, focusing on adiponectin, leptin, and resistin. Project 3 (Birnbaum) investigates the regulation of metabolism by Akt/PKB in beta cell and the brain. Project 4 (Kaestner) addresses the role of the Foxa family of transcription factors, as well as coactivators, in liver metabolism. Project 5 (Staffers) focuses on regulation of pancreatic development and differentiation by the homeodomain transcription factor PDX. Each individual project addresses an important hypothesis using molecular and genetic tools, including in vivo mutational analysis. A particularly exciting aspect of this proposal is its tremendous potential for synergism. Frequent interactions will maximize the opportunities for new discoveries related to obvious or surprising interactions between this variety of molecules and metabolic tissues. These interactions will be facilitated by a collaborative environment at the University of Pennsylvania; the close physical proximity of the investigators; an administrative core that coordinates frequent meetings among the investigators and with scientific visitors; an outstanding morphology core in a dedicated central space that encourages physical and intellectual interactions via the technical director and shared personnel; and embryonic stem cell core and metabolic phenotyping cores that facilitate interactions and rapid dissemination of new results, techniques, and ideas. The proposed studies will address major and specific questions relevant to diabetes and metabolic diseases. At the same time, the specific investigators, environment, and format of this proposal facilitate interactions that should enhance the discovery process. There is an excellent likelihood that advances made by this program project group will have a positive impact on the epidemics of diabetes and metabolic diseases that are ravaging our society.

越来越多地认为糖尿病受到复杂的遗传和代谢因素的影响 多个器官和分子。一个重要的分子可以直接或间接控制 其他分子和多个组织。成人组织的功能显然取决于其历史， 即，其分化和发育以及从其他组织发出的信号和 环境。该计划项目赠款涉及五名杰出调查员，每个调查员都专注于特定 调节特定组织的发育和代谢功能的分子。项目1（拉扎尔） 解决了抗脂肪细胞分泌因子（脂肪因子），胰岛素抵抗和胰岛素抵抗的作用 动脉粥样硬化。项目2（Ahima）研究了中枢神经系统在介导的作用 脂肪因子的代谢作用，重点是脂联素，瘦素和抗素。项目3（Birnbaum） 研究了Beta细胞和大脑中AKT/PKB对代谢的调节。项目4（Kaestner） 介绍了FoxA转录因子家族以及共激活因子在肝脏代谢中的作用。 项目5（工作人员）着重于对胰腺发展和分化的调节 同源域转录因子PDX。每个项目都使用一个重要的假设 分子和遗传工具，包括体内突变分析。一个特别令人兴奋的方面 提案是其协同作用的巨大潜力。频繁的互动将最大化 与这种各种分子与代谢之间的明显或令人惊讶相互作用有关的新发现 组织。这些互动将由大学的协作环境促进 宾夕法尼亚州；调查人员的亲密接近；协调的行政核心 调查人员和科学访客之间经常会议；一个出色的形态核心 专门的中心空间，通过技术总监和 共享人员；以及促进相互作用的胚胎干细胞核和代谢表型核心 以及快速传播新结果，技术和思想。拟议的研究将针对专业和 与糖尿病和代谢疾病有关的具体问题。同时，特定的调查人员， 该提案的环境和格式有助于增强发现过程的相互作用。 这个计划项目组的进步很有可能会产生积极的影响 关于破坏我们社会的糖尿病和代谢疾病的流行病。