Regulation of glucose and glycogen metabolism during and after exercise

Abstract

Utilization of carbohydrate in the form of intramuscular glycogen stores and glucose delivered from plasma becomes an increasingly important energy substrate to the working muscle with increasing exercise intensity. This review gives an update on the molecular signals by which glucose transport is increased in the contracting muscle followed by a discussion of glycogen mobilization and synthesis by the action of glycogen phosphorylase and glycogen synthase, respectively. Finally, this review deals with the signalling relaying the well-described increased sensitivity of glucose transport to insulin in the post-exercise period which can result in an overshoot of intramuscular glycogen resynthesis post exercise (glycogen supercompensation).

Figure 1. Glucose utilization in the working muscle is increased through increased delivery and uptake of plasma glucose and increased glycogenolysis

Transport of glucose across the sarcolemma and T-tubular membranes is determined by the amount of contraction- and insulin-responsive glucose transporter 4 (GLUT4) proteins in the outer membrane. This magnitude of glucose transport response with contraction correlates with work intensity with evidence suggesting the involvement of kinases like AMPK, p38 MAPK and SNARK whereas Ca²⁺ activated proteins are probably required but likely to be insufficient to stimulate glucose transport. Allosteric and covalent regulation increases both glycogen mobilization by glycogen phosphorylase (GP) and resynthesis by glycogen synthase (GS) simultaneously during exercise by altering enzyme activity and/or location. GP may also be regulated by the availability of its substrates glycogen and inorganic phosphate (P_i). Depending on the work intensity and duration, glucose-6-phosphate (G-6-P), an important allosteric inhibitor of GP and stimulator of GS, may increase.

Figure 2. Augmented glycogen resynthesis post-exercise is explained to a large part by sensitization of the insulin-stimulated glucose transport response and glycogen synthase activation

Although some signalling proteins display a prolonged increase in phosphorylation for many hours after exercise, perhaps contributing to insulin sensitization, many insulin-signalling endpoints seem unaffected by prior contraction. Mobilization of GLUT4 during contraction may cause a subsequent sorting into a more insulin-responsive pool or position. Insulin sensitization may require permissive input from one or more unidentified serum factors. Increased amounts of transported glucose are converted to glucose-6-phosphate (G-6-P) which allosterically increases glycogen synthase and inhibits phosphorylase activity, respectively. High glycogen shows a correlation with decreased insulin-stimulated glucose transport and glycogen synthase inactivation but whether this is a causal relationship remains unclear.