CORE--Clinical Core

这个以患者为导向的多学科项目的总体目标是确定线粒体功能障碍在人类胰岛素抵抗和其他相关代谢紊乱的发病机制中的作用。该计划的所有三个项目都需要招募和表征线粒体异常患者进行代谢表征和遗传研究。在临床中心志愿者的招募、筛选将集中进行。Core将为本项目下的每项研究提供磁共振和稳定同位素输注研究的专业临床支持。通过集中这一核心，我们将能够为这些磁共振输液和钳夹研究提供所需的最高水平的技术和临床专业知识，并通过消除重复来提高效率。具体来说，该核心将：(1)筛选、招募并进行高胰岛素-正血糖钳夹研究，在年轻的瘦胰岛素抵抗后代和年龄-体重-活动匹配的对照受试者和mt tRNA突变患者中进行项目1,2,3,（II）筛选，招募已知线粒体tRNA突变与高血压相关的患者进行项目1,2,3和（III）筛选，招募健康的老年受试者进行项目3。此外，该核心将为稳定同位素输注研究提供专门的临床支持，该研究将在4.0T磁共振光谱仪内进行，以评估项目1、2和3中肌肉、肝脏和大脑中线粒体活性的组织特异性比率。

The overall objective of this multidisciplinary patient oriented Program Project is to determine the role of mitochondrial dysfunction in the pathogenesis of insulin resistance and other related metabolic disorders in humans. All three projects in the Program entail recruitment and characterization of patients with mitochondrial abnormalities for metabolic characterization and genetic studies. In the Clinical Core volunteer recruitment, and screening will be centralized. The Core will provide specialized clinical support for magnetic resonance and stable isotope infusion studies for each of the studies under this Program Project. By centralizing this core we will be able to provide the highest level of technical and clinical expertise required for these magnetic resonance infusion and clamp studies as well as increased efficiency by eliminating duplication. Specifcally this core will: (I) screen, recruit and perform hyperinsulinemic-euglycemic clamp studies in young lean insulin resistant offspring and age-weight-activity matched control subjects and patients with mt tRNA mutations for Projects 1, 2, 3, (II) screen and recruit patients with a known mitochondrial tRNA mutation that is associated with hypertension for projects 1, 2, 3 and (III)screen and recruit healthy elderly subjects for project 3. In addition this core will provide specialized clinical support for stable isotope infusion studies that will be performed inside the 4.0T magnetic resonance spectrometer in order to assess tissue specific rates of mitochondrial activitiy in muscle, liver and brain for Projects 1,2 & 3. This clinical core is thus an essential resource that is required to complete the research proposed in Projects 1,2 & 3.