SUBSTRATE SUPPLY DURING EXERCISE

这是一个建议，以调查的作用，乳酸作为一个氧化 运动过程中的代谢底物和代谢前体。 我们的经营 这一假说被称为"乳酸穿梭机"。"我们假设， 运动时，乳酸在糖原分解和糖酵解的高部位形成 并通过呼吸道到达高细胞呼吸和再生的部位。 氚和血浆。 生产地点包括快速糖酵解 肌肉纤维，接受肾上腺素刺激的纤维，k，可能， 肝脏（胰高血糖素刺激）。 移除部位包括红色骨骼肌 纤维心脏和肝脏 此外，我们假设乳酸是一个主要的 对维持血液循环至关重要的促血管生成前体 葡萄糖稳态 此外，我们假设乳酸穿梭 提供了一种机制，通过该机制， 有组织的和规范的。 特别是，我们计划研究其急性和 慢性运动（训练）影响乳酸穿梭。 为这些 目的，我们提出了一系列动力学同位素示踪研究，以及 输注未标记材料以及阻滞剂和抑制剂的研究 在实验室老鼠。 通过这种方法，我们希望阐明激素和 其它信号协调穿梭机构。 这些研究报告将 辅以运用运动技术和方法的研究， 生理学和生物化学。 我们计划分离肌膜囊泡， 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LDH是否与 肌肉纤维类型之间的差异以及对训练的反应， 乳酸穿梭机的功能。 此外， 糖酵解，TCA循环和电子传递链酶和组分， 骨骼肌、心脏和肝脏将在体外进行研究， 体内代谢动力学的机理解释。

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.