The impact of methylxanthines on muscle carbohydrate metabolism

This thesis investigates the impact of methylxanthines on skeletal muscle carbohydrate metabolism in humans at rest and during exercise, and examined the presence of adenosine receptors in rodent and human skeletal muscle. The purpose of study 1 was to investigate the ergogenic potential of theophylline and its effect on skeletal muscle metabolism and compare it to responses elicited by caffeine during endurance exercise. Theophylline significantly enhanced endurance exercise (80% VO2 max) performance compared to placebo, although not as consistently as caffeine. Some of the metabolic effects of theophylline (such as lipolytic responses and increases in muscle cAMP (indicative of a methylxanthine-induced antagonism of adenosine receptors)), were greater following the administration of this methylxanthine compared to caffeine. The purpose of study 2 was to examine the effect of caffeine on glucose uptake in resting human subjects using a hyperinsulinemic euglycemic clamp technique. Caffeine administration resulted in a 24% decrease in glucose uptake and a 35% decrease in carbohydrate storage compared to placebo. These findings support the functional metabolic role that has been defined for adenosine in skeletal muscle. The purpose of the final study in this thesis was to investigate the presence of A1 and A2a adenosine receptors in oxidative and glycolytic muscle fibers using rat skeletal muscle in addition to investigating the existence of these receptors in human skeletal muscle. The initial part of this study used specific A1 and A2 adenosine receptor antagonists to measure cAMP responses to these compounds (an amplified physiological response as a result of receptor binding). Data from these experiments demonstrated the functional presence of A2, but not A1 receptors in oxidative rodent skeletal muscle. To expand on these findings, western blotting techniques were used to further investigate A1 and A 2a receptors in rodent and human skeletal muscle. These experiments provided evidence for the presence of both A1 and A2a receptor subtypes in rodent and human skeletal muscle.;Thus, the main findings from these studies were the alterations in resting skeletal muscle metabolism that suggested a methylxanthine-induced antagonism of adenosine receptors and the presence of adenosine, receptors in both human and rodent skeletal muscle.