Regulation of human skeletal muscle glucose metabolism in response to exercise

骨骼肌对摄入的营养物质(如碳水化合物和脂肪)的吸收、利用和储存是不可或缺的，使其成为调节血糖动态平衡和全身能量代谢的基本组织。众所周知，运动过程中对能量的需求会增加，这会对骨骼肌产生持续数小时甚至数天的影响。例如，运动可以增加骨骼肌摄取碳水化合物的能力长达48小时；然而，不同运动刺激影响这种反应的幅度和持续时间的机制尚不完全清楚。我的NSERC研究计划将调查运动如何改变人类骨骼肌碳水化合物代谢的调节，重点是调节骨骼肌葡萄糖(糖)摄取的机制。这个话题传统上是通过长时间的中等强度运动训练(“耐力训练”)来探索的，但我之前的研究表明，令人惊讶的是，少量的间歇性高强度肌肉收缩(“高强度间歇训练”)也能引起类似的反应。在这项工作的基础上，我们将通过改变运动量(例如，运动强度和/或持续时间)或应用改变运动诱导的肌肉燃料利用的营养干预来施加独特的代谢扰动，以检查哪些因素会影响运动后的肌肉葡萄糖代谢。参与者将在运动后的特定时间点饮用高糖饮料，以测试肌肉在单次运动后对碳水化合物的反应。在运动前后和饮用含糖饮料后，将采集血液样本和腿部肌肉活检，以测量与碳水化合物代谢有关的底物、蛋白质和酶。研究将在健康的女性和男性中进行，以确定生物性别是否会影响运动反应。我们还将在“已训练”和“未训练”状态下进行实验，以测试定期运动训练是否能改变单次运动的效果。这一研究计划将提供高度受控的人体运动和营养实验，并辅之以肌肉代谢的详细特征。重要的是，拟议的研究将产生关于运动、营养和生物性别如何影响人类骨骼肌葡萄糖代谢的基本机械性信息。这一新知识将推动人类生理学和骨骼肌能量代谢领域的发展，并可能被用来改进治疗和/或康复策略，以对抗人类全身和骨骼肌代谢障碍。此外，该研究项目将为受训者提供一个多学科的环境，让他们发展独特的技能，这些技能将被用来推动加拿大学术界或工业界研究和创新的未来。

Skeletal muscle is indispensable for the uptake, utilization and storage of ingested nutrients (e.g., carbohydrates and fats), making it a fundamental tissue in the regulation of blood glucose homeostasis and whole-body energy metabolism. It is well known that energy demands increase during exercise, which can impose lasting effects on skeletal muscle that persist for hours or even days following. For example, exercise can increase the capacity of skeletal muscle to take in carbohydrates for up to 48 hours; however the mechanisms by which different exercise stimuli influence the magnitude and duration of this response is incompletely understood. My NSERC research program will investigate how exercise alters the regulation of skeletal muscle carbohydrate metabolism in humans with a focus on the mechanisms that regulate skeletal muscle glucose (sugar) uptake. This topic has traditionally been explored using prolonged, moderate-intensity exercise training ("endurance training"), but my previous research has shown that similar responses can be induced with a surprisingly small amount of intermittent, high-intensity muscle contraction ("high-intensity interval training"). To build on this work, we will impose unique metabolic perturbations by altering exercise amount (e.g., intensity and/or duration of exercise) or applying nutritional interventions that alter exercise-induced muscle fuel utilization, to examine what factors influence muscle glucose metabolism following exercise. Participants will consume a high-sugar beverage at certain time points after exercise in order to "test" how muscle responds to carbohydrate following a single session of exercise. Blood samples and leg muscle biopsies will be taken before and after exercise and after consuming the sugar beverage to measure substrates, proteins and enzymes involved in carbohydrate metabolism. Studies will be performed in both healthy women and men to determine if biological sex impacts exercise responses. We will also conduct experiments in the "trained" and "untrained" state to test if regular exercise training modifies the effects of a single session of exercise. This program of research will deliver highly controlled human exercise and nutrition experiments that are complimented by detailed characterization of muscle metabolism. Importantly, the proposed studies will generate basic, mechanistic information on how exercise, nutrition and biological sex influence skeletal muscle glucose metabolism in humans. This new knowledge will advance the fields of human physiology and skeletal muscle energy metabolism, and may also be leveraged to improve therapies and/or rehabilitation strategies that combat whole-body and skeletal muscle metabolic dysfunction in humans. In addition, this research program will provide a multidisciplinary environment for trainees to develop a unique skillset that will be leveraged to advance the future of Canadian research and innovation in academia or industry.