KINETICS OF MUSCLE METABOLISM BY POSITRON TRACERS

描述(改编自申请人的摘要)：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，第一，与使用(18F)2-脱氧-2- 氟葡萄糖(FDG)来评估葡萄糖摄取，其次， 葡萄糖作为一种基本的燃料。申请者将把连续的 应用FDG评价心脏工作准备中的葡萄糖摄取 它执行的是近乎生理的工作。第一个具体目标是 明确己糖激酶易位与葡萄糖的关系 代谢和FDG。具体地说，申请者将定义因素 对己糖激酶相对亲和力的变化负责 葡萄糖与FDG的比较。第二个具体目标是基于 观察到两种不同的葡萄糖摄取模式： 立即和延迟。申请人假设立即发生的 对竞争底物的反应反映了葡萄糖的调节 转运蛋白分子在原位，而葡萄糖的延迟反应 对胰岛素或肾上腺素的摄取反映转运蛋白的募集 分子(过剩4)到肌膜。这两个回应将是 利用葡萄糖示踪研究结合 GLUT膜定位的免疫印迹分析4.第三 特定的目标将描绘葡萄糖摄取对不同种类的反应 在表现出协调的多部位调节的系统中的刺激 葡萄糖代谢。这项工作将定义两者之间的关系 葡萄糖转运、糖酵解通量和糖原代谢，摄取 一种独特的同时测定方法的优势 糖原的合成和降解。第四个具体目标涉及 通过补充克雷布斯循环，葡萄糖作为心脏的基本燃料 中间体，除了用作可氧化的底物外。 Krebs循环的葡萄糖摄取、收缩功能和恢复 将结合FDG和13C-核磁共振波谱进行定量。

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.