Regulation of human skeletal muscle glucose metabolism in response to exercise

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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.