Mechanism of enhanced insulin sensitivity in athletes increased blood flow, muscle glucose transport protein (GLUT-4) concentration, and glycogen synthase activity

We examined the mechanisms of enhanced insulin sensitivity in 9 male healthy athletes (age, 25±1 yr; maximal aerobic power [V O₂max], 57.6±1.0 ml/kg per min) as compared with 10 sedentary control subjects (age, 28±2 yr; VO₂max, 44.1±2.3 ml/kg per min). In the athletes, whole body glucose disposal (240-min insulin clamp) was 32% (P < 0.01) and non-oxidative glucose disposal (indirect calorimetry) was 62% higher (P < 0.01) than in the controls. Muscle glycogen content increased by 39% in the athletes (P < 0.05) but did not change in the controls during insulin clamp. VO₂max correlated with whole body (r = 0.60, P < 0.01 ) and nonoxidative glucose disposal (r = 0.64, P < 0.001). In the athletes forearm blood flow was 64% greater (P < 0.05) than in the controls, whereas their muscle capillary density was normal. Basal blood flow was related to VO₂max (r = 0.63, P < 0.05) and glucose disposal during insulin infusion (r = 0.65, P < 0.05). The forearm glucose uptake in the athletes was increased by 3.3-fold (P 0.01) in the basal state and by 73% (P < 0.05) during insulin infusion. Muscle glucose transport protein (GLUT-4) concentration was 93% greater in the athletes than controls (P < 0.01) and it was related to VO₂max(r = 0.61,P < 0.01) and to whole body glucose disposal (r = 0.6U, P < 0.01). Muscle glycogen synthase activity was 33% greater in the athletes than in the controls (P < 0.05), and the basal glycogen synthase fractional activity was closely related to blood flow (r = 0.88, P < 0.001). In conclusion: (a) athletes are characterized by enhanced muscle blood flow and glucose uptake. (b) The cellular mechanisms of glucose uptake are increased GLUT-4 protein content, glycogen synthase activity, and glucose storage as glycogen. (c) A close correlation between glycogen synthase fractional activity and blood flow suggests that they are causally related in pro-moting glucose disposal.