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: 7288251
• 负责人: MITCHELL A. LAZAR
• 金额: $ 188.51万
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7288251
• 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.

越来越多的人认识到糖尿病受复杂的遗传和代谢因素的影响， 多种器官和分子一个重要的分子可以直接或间接地控制细胞的功能。 其他分子和多种组织。成年组织的功能显然取决于其历史， 也就是说，它的分化和发展，以及从其他组织发出的信号， 环境该计划项目赠款涉及五名杰出的研究人员，每个人都专注于一个特定的 调节特定组织发育和代谢功能的分子。项目1（拉扎尔） 阐述了一种新的脂肪细胞分泌因子（脂肪因子）-在胰岛素抵抗中的作用， 动脉粥样硬化项目2（Ahima）研究中枢神经系统在介导 脂肪因子的代谢作用，重点是脂联素、瘦素和瘦素。项目3（伯恩鲍姆） 研究Akt/PKB在β细胞和脑中的代谢调节。项目4（Kaestner） 阐述了Foxa家族转录因子以及共激活因子在肝脏代谢中的作用。 项目5（Staffers）重点关注胰腺发育和分化的调控， 同源域转录因子PDX。每一个单独的项目解决一个重要的假设， 分子和遗传工具，包括体内突变分析。其中一个特别令人兴奋的方面是， 这一建议的一个重要特点是其巨大的协同潜力。频繁的互动将最大限度地增加机会， 新的发现与这些不同的分子和代谢之间明显或令人惊讶的相互作用有关， 组织中这些互动将通过大学的协作环境来促进。 宾夕法尼亚州;调查人员的密切物理接近;协调的行政核心 研究人员和科学访问者之间的频繁会议;一个杰出的形态核心， 专门的中央空间，通过技术总监鼓励身体和智力的互动， 共享人员;以及促进相互作用的胚胎干细胞核心和代谢表型核心 以及新成果、技术和思想的快速传播。拟议的研究将涉及主要和 与糖尿病和代谢疾病相关的具体问题。与此同时，具体的调查人员， 环境，以及本提案的格式促进了应增强发现过程的交互。 该计划项目组取得的进展极有可能产生积极影响 糖尿病和代谢性疾病的流行正在肆虐我们的社会。