SUBSTRATE SUPPLY DURING EXERCISE

这是一项研究乳酸作为一种可氧化物质的作用的建议。 运动过程中的底物和糖异生前体。我们的运营 假说被称为“乳酸穿梭”。我们假设在 运动时，在高糖原分解和糖酵解的部位形成乳酸 到达高细胞呼吸和糖异生的部位，通过 间质和血浆。产生部位包括快速糖酵解 肌肉纤维，接受肾上腺素刺激的纤维，k和可能的， 肝脏(高血糖素刺激)。移除部位包括红色骨骼肌 纤维、心脏和肝脏。此外，我们假设乳酸是一种主要的 糖异生前体对维持血液至关重要 葡萄糖动态平衡。此外，我们假设乳酸穿梭机 提供了一种机制，通过这种机制，组织内和组织间的新陈代谢 有组织、有管理。特别是，我们计划研究如何尖锐和 长期运动(训练)会影响乳酸穿梭。为了这些 目的，我们提出了一系列动力学同位素示踪研究，以及 使用未标记物质、阻滞剂和抑制剂输注的研究 在实验室的大鼠身上。通过这种方法，我们希望能阐明荷尔蒙和 其他协调穿梭机构的信号。这些研究将是 辅以使用锻炼技术和方法的研究 生理学和生物化学。我们计划分离肌膜小泡和 描述组织差异和训练对乳酸的影响 传送器。我们还计划确定线粒体乳酸脱氢酶是否不同 肌肉纤维类型和对训练的反应之间的关系 乳酸穿梭机的运作。此外，该组织的活动 糖酵解、TCA循环和电子传递链酶及其组分 骨骼肌、心脏和肝脏将在体外进行研究，以提供 体内代谢物动力学的机理解释。

This is a proposal to investigate the roles of lactate as an oxidizable substrate and gluconeogenic precursor during exercise. Our operating hypothesis is termed "THE LACTATE SHUTTLE." We hypothesize that during exercise, lactate is formed at sites of high glycogenolysis and glycolysis and reaches sites of high cellular respiration and gluconeogenesis via the interstitium and plasma. Sites of production include fast glycolytic muscle fibers, fibers undergoing epinephrine stimulation,k and possibly, liver (glucagon stimulation). Removal sites include red skeletal muscle fibers, heart, and liver. Moreover, we hypothesize that lactate is a major gluconeogenic precursor essentially important for the maintenance of blood glucose homeostasis. Moreover we hypothesize that the lactate shuttle provides a mechanism through which metabolism within and between tissues is organized and regulated. In particular, we plan to study how acute and chronic exercise (training) affects the lactate shuttle. For these purposes, we propose a series of kinetic isotope tracer studies, as well as studies using infusion of unlabeled materials and blockers and inhibitors in laboratory rats. By this means we hope to elucidate the hormonal and other signals coordinating the shuttle mechanism. These studies will be complemented by studies using the techniques and approaches of exercise physiology and biochemistry. We plan to isolate sarcolemmal vesicles and to describe tissue differences and training effects on the lactate transporter. We plan also to determine if mitochondrial LDH differs between muscle fiber types and responds to training in ways to explain functioning of the lactate shuttle. Moreover, the activities of glycolytic, TCA cycle and electron transport chain enzyme and components in skeletal muscle, heart and liver will be studied in vitro to provide a mechanistic explanation of metabolite kinetics in vivo.