KINETICS OF MUSCLE METABOLISM BY POSITRON TRACERS

正电子示踪剂的肌肉代谢动力学

• 批准号: 2445190
• 负责人: HEINRICH TAEGTMEYER
• 金额: $ 26.99万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2445190
• 关键词: bioenergetics; chemical kinetics; enzyme substrate; glucose metabolism; glucose transport; glucose transporter; heart metabolism; hexokinase; insulin; isolation perfusion; muscle metabolism; nuclear magnetic resonance spectroscopy; positron emission tomography; sarcolemma; triglycerides; western blottings

DESCRIPTION (adapted from the applicant's abstract): The applicant proposes to examine the role of glucose as an energy providing substrate in two broad areas relating, first, to the use of (18F) 2-deoxy-2- fluoroglucose (FDG) to assess glucose uptake, and secondly, the role of glucose as an essential fuel. The applicant would combine the continuous assessment of glucose uptake by FDG with a working heart preparation which performs near physiologic work. The first specific aim will define the role of hexokinase translocation in relation to glucose metabolism and FDG. Specifically, the applicant will define the factors responsible for changes in the relative affinities of hexokinase for glucose as compared to FDG. The second specific aim is based on the observation of two qualitatively different patterns of glucose uptake: immediate and delayed. The applicant hypothesizes that the immediate response to competing substrates reflects regulation of glucose transporter molecules in situ, while the delayed response of glucose uptake to insulin or epinephrine reflects recruitment of transporter molecules (GLUT 4) to the sarcolemma. The two responses will be delineated with the use of tracer studies of glucose in conjunction with immunoblot analysis of the membrane localization of GLUT 4. The third specific aim will delineate the responses of glucose uptake to a variety of stimuli in a system exhibiting coordinated multi-site regulation of glucose metabolism. This work will define the relationship between glucose transport, glycolytic flux, and glycogen metabolism, taking advantage of a unique approach to the simultaneous determinations of glycogen synthesis and degradation. The fourth specific aim concerns glucose as an essential fuel for the heart, by replenishing Krebs cycle intermediates, in addition to serving as an oxidizable substrate. Glucose uptake, contractile function and anaplerosis of the Krebs cycle will be quantitated by combining FDG and 13C-NMR spectroscopy.

描述（改编自申请人摘要）：申请人 建议研究葡萄糖作为能量提供底物的作用 在两个广泛的领域中，首先，涉及（18F）2-脱氧-2- 氟葡萄糖（FDG）评估葡萄糖摄取，其次， 葡萄糖作为基本燃料。申请人将联合收割机 心脏工作准备时FDG对葡萄糖摄取的评估 其执行接近生理的工作。第一个具体目标将 确定己糖激酶转位与葡萄糖相关的作用 代谢和FDG。具体而言，申请人将确定 负责改变己糖激酶对 与FDG相比，第二个具体目标是基于 观察到两种性质不同的葡萄糖摄取模式： 即时和延迟。申请人假设， 对竞争底物的反应反映了葡萄糖的调节 转运分子原位，而葡萄糖的延迟反应 对胰岛素或肾上腺素的摄取反映了转运蛋白的募集 分子（GLUT 4）的肌膜。这两个答案将是 使用葡萄糖示踪剂研究结合 GLUT 4的膜定位的免疫印迹分析。第三 具体的目标将描绘葡萄糖摄取对各种 系统中的刺激表现出协调的多部位调节， 葡萄糖代谢这项工作将确定之间的关系 葡萄糖转运、糖酵解通量和糖原代谢， 同时测定的独特方法的优点 糖原合成和降解。第四个具体目标是 葡萄糖作为心脏的基本燃料，通过补充Krebs循环 中间体，除了作为可氧化的底物。 葡萄糖摄取、收缩功能和克雷布斯循环的回补 将通过结合FDG和13 C-NMR光谱进行定量。