Exercise is a metabolic challenge with a synchronized endocrine response (
14). Metabolic responses to exercise are determined primarily by the intensity, duration, and environmental conditions (i.e. temperature, humidity, time of day) (
1). Skeletal muscle plays a critical role in glycemic control and metabolic homeostasis and is the predominant site of glucose disposal under insulin-stimulated conditions (
15,
16). Skeletal muscle is also the largest glycogen storage organ, having an approximate 4-fold greater glycogen storage capacity than the liver (
15). AMP-activated protein kinase (AMPK) is a serine/threonine kinase that serves as a sensor of cellular energy status (
15,
17). AMPK modulates cellular metabolism via phosphorylation of metabolic enzymes (
18) and transcriptional regulation (
19,
20). AMPK activation is chiefly regulated by cellular energy deficits, which are reflected by increases in the adenosine monophosphate (AMP)/adenosine triphosphate (ATP) and creatine (Cr)/phosphocreatine (PCr) ratios (
21). Given the high rate of ATP turnover during muscle contraction, exercise increases AMPK phosphorylation and enzymatic activity in an intensity-dependent manner (
22,
23). AMPK activation acts to conserve ATP by inhibiting biosynthetic and anabolic pathways, while simultaneously stimulating catabolic pathways to restore cellular energy stores (
21). In skeletal muscle, acute AMPK activation suppresses glycogen (
18) and protein synthesis (
24), but promotes glucose transport (
25) and lipid metabolism (
26).
Muscles use glucose as their primary source of fuel in the initial stages of exercise (
14). During moderate-intensity exercise (40% - 59% of maximal oxygen consumption [VO
2 max] or 55% - 69% of maximal heart rate), the fuel for muscular contraction is gained almost exclusively from aerobic metabolism- by using a mixture of carbohydrate (CHO) from muscle glycogen stores and circulating free fatty acids (FFA) as fuel (
1). Most endurance sports are performed within the moderate-intensity range (i.e. long-distance running and cycling) (
1). As muscle glycogen stores are depleted, a balance develops between glucose production (primarily via hepatic glycogenolysis (
27)) and glucose uptake by exercising muscle (
14). Insulin secretion concurrently falls (
28,
29) as muscle glucose uptake increases due to exercise stimulating the translocation of GLUT-4 receptors to the cell surface (
30). A slight increase in catecholamines combined with the decrease of insulin promotes lipolysis in exercise, permitting the use of FFA as fuel (
14), and later gluconeogenesis (
31,
32).
High-intensity exercise (85 to 100% VO
2 max or greater than 90% maximal heart rate), sustained for 10 to 30 minutes or intermittent bouts of 3 to 5 minutes, is common in team-oriented sports, such as lacrosse, football, hockey, soccer, track and field, and swimming (
1). Exercise to VO
2 max is primarily sustained by aerobic metabolism, including oxidative phosphorylation and, to a lesser extent, beta oxidation (
1). High-intensity, supramaximal-effort (> VO
2 max) activities sustained for only 3 to 30 seconds, such as sprinting, utilize the anaerobic energy system. In either scenario, high-intensity exercise is highly dependent on glucose as fuel, derived from either hepatic or muscle glycogenolysis (
1). Additionally, exercise at high-intensity is characterized by marked lactate accumulation and a substantial increase in catecholamine concentrations, approximately 14- to 18-folds above basal levels (
33).
Once exercise stops, insulin levels rapidly increase both in response to high BG levels and removal of circulating catecholamines (
1). As a result, hyperglycemia and hyperinsulinemia combine postexercise to provide ideal homeostatic metabolic conditions for the replenishment of muscle glycogen (
14). This promotes rapid recovery and primes the athlete for repeated bouts of high-intensity exercise.