SummaryWith the cessation of exercise, glycogen repletion begins to take place rapidly in skeletal muscle and can result in glycogen levels higher than those present before exercise. Understanding the rate-limiting steps that regulate glycogen synthesis will provide us with strategies to increase the resynthesis of glycogen during recovery from exercise, and thus improve performance.Given the importance of muscle glycogen to endurance performance, various factors which may optimise glycogen resynthesis rate and insure complete restoration have been of interest to both the scientist and athlete. The time required for complete muscle glycogen resynthesis after prolonged moderate intensity exercise is generally considered to be 24 hours provided ≈500 to 700g of carbohydrate is ingested. Muscle glycogen synthesis rate is highest during the first 2 hours after exercise. Ingestion of 0.70g glucose/kg bodyweight every 2 hours appears to maximise glycogen resynthesis rate at approximately 5 to 6 µmol/g wet weight/h during the first 4 to 6 hours after exhaustive exercise. Further enhancement of glycogen resynthesis rate with ingestion of greater than 0.70g glucose/kg bodyweight appears to be limited by the constraints imposed by gastric emptying. Ingestion of glucose or sucrose results in similar muscle glycogen resynthesis rates while glycogen synthesis in liver is better served with the ingestion of fructose. Also, increases in muscle glycogen content during the first 4 to 6 hours after exercise are greater with ingestion of simple as compared with complex carbohydrate.Glycogen synthase activity is a key component in the regulation of glycogen resynthesis. Glycogen synthase enzyme exists in 2 states: the less active, more phosphorylated (D) form which is under allosteric control of glucose-6-phosphate, and the more active, less phosphorylated (I) form which is independent of glucose-6-phosphate. There is generally an inverse relationship between glycogen content in muscle and the percentage synthase in the activated (I) form. Exercise and insulin by themselves activate glycogen synthase by conversion to glycogen synthase I. Although small changes in the activity ratio (% I form) can lead to large changes in the rate of glycogen synthesis, glycogen synthase I appears to increase very little (≈25%) in response to glycogen depletion and returns to pre-exercise levels as glycogen levels return to normal. Thus glycogen resynthesis, which may increase 3- to 5-fold, may also be influenced by glucose-6-phosphate, which can activate glycogen synthase in the D form.There is considerable evidence that glucose transport across the cell membrane is the rate limiting step in the synthesis of muscle glycogen. Thus, regulation of glucose transport may ‘set the pace’ for glycogen resynthesis after exercise. Contractile activity increases the permeability of muscle to glucose even in the absence of insulin and this increase in glucose transport persists for several hours after cessation of exercise. Increased glucose transport into muscle may persist for 16 to 20 hours following exercise in rats if carbohydrate intake is restricted. This suggests that glucose transport may be regulated by glycogen concentration. However, the rate of glucose transport is not increased when muscle glycogen concentration is reduced by an overnight fast, suggesting that contractile activity provides an important stimulus linking glucose transport and the resynthesis of muscle glycogen. The changes in glucose transport suggest that ingestion of carbohydrate immediately after cessation of exercise should result in the most rapid resynthesis of muscle glycogen.Muscle possesses a unique tissue specific glucose transporter protein, termed GLUT4, which regulates glucose transport across the muscle cell membrane. Exercise training increases the synthesis of GLUT4 glucose transporters in skeletal muscle. This adaptation, along with a similar increase in glycogen synthase enzyme with training, suggests the ability to increase glycogen stores in the trained state may in part be due to increased numbers of glucose transporters.