Differentiated function of tissues involved in nutrition and metabolism

越来越多的人认识到糖尿病受到复杂的遗传和代谢因素的影响，包括 多个器官和分子。单个重要的分子可能直接或间接地控制着 其他分子和多个组织。成体组织的功能显然取决于它的历史， 即其分化和发育，以及来自其他组织和 环境。该计划项目拨款涉及五名杰出的调查人员，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) 探讨抵抗素，一种新的脂肪细胞分泌因子(脂肪因子)在胰岛素抵抗和 动脉硬化。项目2(Ahima)研究了中枢神经系统在调节 脂肪因子的代谢作用，重点是脂联素、瘦素和抵抗素。项目3(伯恩鲍姆) 研究Akt/PKB对β细胞和脑内代谢的调节。项目4(凯斯特纳) 阐述FOXA转录因子家族以及辅助激活因子在肝脏新陈代谢中的作用。 项目5(工作人员)集中于胰腺发育和分化的调节 同源结构域转录因子PDX。每个单独的项目都解决了一个重要的假设 分子和遗传工具，包括体内突变分析。这其中一个特别令人兴奋的方面 这一提议具有巨大的协同效应潜力。频繁的互动将最大限度地增加 与这种分子和新陈代谢之间明显或令人惊讶的相互作用有关的新发现 纸巾。这些互动将由密歇根大学的协作环境促进 宾夕法尼亚州；调查人员在物理上非常接近；协调的行政核心 研究人员和科学访问者之间的频繁会议；一个杰出的形态学核心 专门的中央空间，鼓励通过技术总监和 共享人员；以及促进互动的胚胎干细胞核心和代谢表型核心 并迅速传播新成果、新技术和新思想。拟议的研究将涉及主要和 与糖尿病和代谢性疾病相关的具体问题。同时，具体的调查人员， 环境和本建议书的格式促进了应加强发现过程的互动。 该方案项目组取得的进展极有可能产生积极影响 关于正在肆虐我们社会的糖尿病和代谢性疾病的流行。

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.