Exercise, muscle glycogen and insulin action

The aim of this thesis was to investigate the influence of muscle glycogen concentration on whole body insulin stimulated glucose uptake in humans and to examine the potential signalling mechanisms responsible for enhanced insulin action in the post exercise period. Untrained male subjects were conditioned to achieve a range of muscle glycogen concentrations via acute exercise or a combination of exercise and diet. The influence of muscle glycogen content on whole body insulin stimulated glucose uptake was determined via hyperinsulinaemic / euglycaemic clamps conducted at rest, 30 min after exercise or 24 hours after exercise. Muscle glycogen content did not influence insulin mediated glucose disposal either 30 min or 24 hrs after exercise when compared with basal. Conventional insulin signalling to muscle glucose uptake and signalling through the p38 MAPK cascade was also largely unaltered by glycogen concentration. Muscle glycogen synthesis was significantly increased in heavily but not moderately glycogen depleted muscle 30 min after exercise. Enhanced muscle glycogen synthesis occurred in line with a significant increase in insulin stimulated GSK-3 serine phosphorylation. This finding suggests that enhanced insulin sensitivity of muscle glycogen synthesis following glycogen depleting exercise may be mediated via a pathway involving alterations in insulin stimulated GSK-3 phosphorylation. In summary, whilst glycogen influences insulin mediated GSK-3 phosphorylation and glycogen synthesis, the findings of the present series of investigations suggest that the role of muscle glycogen in the process of insulin stimulated glucose uptake may not be as important as previously theorised.