MOUSE METABOLIC PHENOTYPING CENTER

小鼠代谢表型中心

• 批准号: 8363893
• 负责人: SHAWN M BURGESS
• 金额: $ 4.82万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363893
• 关键词: Animal Model; Animals; Basic Science; Biological Assay; Cations; Citric Acid Cycle; Computers; Data; Detection; Disease; Fatty acid glycerol esters; Funding; Gluconeogenesis; Glucose; Glycerol; Grant; Hepatic; Life; Liver; Measures; Metabolic; Metabolism; Methods; Modeling; Mus; NMR Spectroscopy; National Center for Research Resources; Non-Insulin-Dependent Diabetes Mellitus; Phenotype; Physicians; Principal Investigator; Protocols documentation; Pyruvate; Recycling; Research; Research Infrastructure; Research Personnel; Resources; Scientist; Series; Source; Techniques; Testing; Tracer; United States National Institutes of Health; cost; design; glucose production; improved; in vivo; oxidation; web site

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 本项目的目的是建立标准的小鼠表型分析技术，以定量评估肝再生，丙酮酸再循环，甘油和克雷布斯循环中间体对葡萄糖产生的贡献，总葡萄糖周转率，柠檬酸循环流量在活动物中使用13 C和2 H示踪剂和NMR光谱的组合。该标准代谢试验提供了现有最全面的肝脏中间代谢分析。它将提供给校内和校外的研究人员有NIDDM或相关疾病的动物模型。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异性代谢技术，包括底物氧化的定量测量、细胞内阳离子的测量和使用13 C富集底物的柠檬酸循环通量。这个表型分析中心的一个独特之处是，输入将来自化学家，物理学家，生理学家，计算机科学家，医生和遗传学家。他们都是公认的13 C同位素分析专家。一台600 MHz NMR光谱仪将专用于该项目。选择用于表型分析的所有小鼠将接受由高级技术人员执行的标准方案;数据将由NMR光谱学家和生物化学家进行分析和解释，并通过交互式网站提供，该网站旨在允许外部研究者测试其同位素异构体数据与替代代谢模型的拟合。基础研究核心将集中在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，并在外部研究人员和中心科学家之间进行接口讨论。