Transgenic mice overexpressing GLUT-1 protein in muscle exhibit increased muscle glycogenesis after exercise

The purpose of the present study was to determine the rates of muscle glyco genolysis and glycogenesis during and after exercise in GLUT-1 transgenic m ice and their age-matched littermates. Male transgenic mice (TG) expressing a high level of human GLUT-1 and their nontransgenic (NT) littermates unde rwent 3 h of swimming. Glycogen concentration was determined in gastrocnemi us and extensor digitorum longus (EDL) muscles before exercise and at 0, 5, and 24 h postexercise, during which food (chow) and 10% glucose solution ( as drinking water) were provided. Exercise resulted in similar to 90% reduc tion in muscle glycogen in both NT (from 11.2 +/- 1.4 to 2.1 +/ 1.3 mu mol/ g) and TG (from 99.3 +/- 4.7 to 11.8 +/- 4.3 mu mol/g) in gastrocnemius mus cle. During recovery from exercise, the glycogen concentration increased to 38.2 +/- 7.3 (5 h postexercise) and 40.5 +/- 2.8 mu mol/g (24 h postexerci se) in NT mice. In TG mice, however, the increase in muscle glycogen concen tration during recovery was greater ito 57.5 +/- 7.4 and 152.1 +/- 15.7 mu mol/g at 5 and 24 h postexercise, respectively). Similar results were obtai ned from EDL muscle. The rate of 2-deoxyglucose uptake measured in isolated EDL muscles was 7- to l0-fold higher in TG mice at rest and at 0 and 5 h p ostexercise. There was no difference in muscle glycogen synthase activation measured in gastrocnemius muscles between NT and TG mice immediately after exercise. These results demonstrate that the rate of muscle glycogen accum ulation postexercise exhibits two phases in TG: 1) an early phase (0-5 h), with rapid glycogen accumulation similar to that of NT mice, and 2) a progr essive increase in muscle glycogen concentration, which differs from that o f NT mice, during the second phase (5-24 h). Our data suggest that the high level of steady-state muscle glycogen in TG mice is due to the increase in muscle glucose transport activity.