MOUSE METABOLIC PHENOTYPING CENTER

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本项目的目的是建立标准的小鼠表型技术，利用13C和2H示踪剂和核磁共振光谱相结合的方法，定量评估肝脏糖异生、丙酮酸循环、甘油和Krebs循环中间体对活体动物葡萄糖产生、总葡萄糖周转和柠檬酸循环通量的贡献。这一标准代谢分析提供了现有最全面的肝脏中间代谢分析。它将向拥有NIDDM或相关疾病动物模型的校内外研究人员提供。除了上述标准代谢谱外，还将为选定的动物模型提供一系列其他表型特定的代谢技术，包括底物氧化的定量测量、细胞内阳离子的测量以及使用富含13C底物的柠檬酸循环通量。这个表型中心的一个独特特点是，输入将来自化学家、物理学家、生理学家、计算机科学家、内科医生和遗传学家。他们都是公认的13C同位素分析专家。一台600 MHz的核磁共振波谱仪将专门用于这一项目。所有被选中进行表型鉴定的小鼠都将接受高级技术人员执行的标准程序；数据将由核磁共振光谱仪和生物化学家进行分析和解释，并通过一个互动网站提供，该网站旨在允许外部研究人员测试他们的同位素异构体数据与替代代谢模型的匹配度。一个基础研究核心将专注于通过间接检测方法提高灵敏度，并开发测量体内脂肪氧化的方法。最后，一个行政核心将协调三个研究核心的活动以及外部调查人员和中心科学家之间的接口讨论。

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. The aim of this project is to establish standard mouse phenotyping techniques to quantitatively evaluate liver gluconeogenesis, pyruvate recycling, the contribution of glycerol and Krebs cycle intermediates to glucose production, total glucose turnover, and citric acid cycle flux in live animals using a combination of 13C and 2H tracers and NMR spectroscopy. This standard metabolic assay provides the most comprehensive existing analysis of hepatic intermediary metabolism. It will be made available to on-campus and off-campus investigators having animal models of NIDDM or related disorders. In addition to the standard metabolic profile described above, a series of other phenotype specific metabolic techniques including a quantitative measure of substrate oxidation, measures of intracellular cations, and citric acid cycle flux using 13C enriched substrates will also be made available for selected animal models. A unique feature of this phenotyping center is that input will come from chemists, physicists, physiologists, computer scientists, physicians, and geneticists. All are recognized experts in 13C isotopomer analysis. A 600 MHz NMR spectrometer will be dedicated to this project. All mice selected for phenotyping will be subjected to a standard protocol performed by high-level technicians; the data will be analyzed and interpreted by NMR spectroscopists and biochemists and made available through an interactive web site designed to allow the external investigators to test a fit of their isotopomer data to alternative metabolic models. A basic research core will focus on improving sensitivity through indirect detection methods and develop methods to measure fat oxidation in vivo. Finally, an administrative core will coordinate the activities of the three research cores and interface discussions between external investigators and center scientists.