Training-Induced Enhancement of Insulin Action in Human Skeletal Muscle: The Influence of Aging

Abstract
Age-induced reduction of whole body insulin action has been attributed to decreased insulin action in skeletal muscle. Physical training improves insulin action, but the effect has never been investigated specifically in aged human skeletal muscle. Seven young men [age: 23 ± 1 yr (mean ± SE; range, 21–24 yr); weight: 70 ± 1 kg; body fat: 8 ± 1%] and eight aged men [59 ± 1 yr (range, 58–64 yr); 83 ± 2 kg; 20 ± 2%] performed one-legged bicycle training on a modified ergometer cycle for 10 weeks, 6 days/week, at 70% of V02 peak. Glucose clearance rates in whole body and leg were measured 16 hr after training by a hyperinsulinemic (28, 88, and 480 mU·min−1·m−2), isoglycemic clamp combined with leg balance technique. Peak oxygen uptake during the bicycle test was always lower (p < .05) in aged vs. young subjects. Furthermore, VO2 peak was higher after training in trained (T) vs. untrained (UT) (p < .05) legs. Whole body glucose clearance rate was lower in aged vs. young subjects (p < .05) when expressed per kg body weight, but similar when expressed relative to fat free mass. Leg blood flow was always lower in aged vs. young men (p < .05). At basal and during insulin infusion, leg blood flow in young men did not differ significantly in T vs. UT legs (maximum insulin: 81 ± 7 vs. 71 ± 5 ml·min−1·kg leg−1), while in aged subjects it increased (p < .05) with training (maximum insulin: 57 ± 5 vs. 48 ± 5 ml·min−1·kg leg−1). Leg glucose extraction was always higher in aged vs. young men during the two last clamp steps (p < .05). Furthermore, leg glucose extraction was increased by training in young (p < .05) but not significantly in aged subjects. Leg glucose clearance rates increased (p < .05) with training and was similar in aged men (T: 1 ± 1, 8 ± 1, 21 ± 2, and 24 ± 2; UT: 1 ± 1, 6 ± 1, 14 ± 2, and 20 ± 2 ml·min−1·kg leg−1) and young men (T: 1 ± 1, 12 ± 3, 23 ± 3, and 26 ± 3; UT: 1 ± 1, 8 ± 2, 17 ± 2, and 21 ± 2 ml·min−1·kg leg−1). Therefore, insulin action in muscle is not reduced by aging. At high insulin concentrations, the leg blood flow is lower, whereas glucose extraction is higher in aged compared with young men. Training increases overall insulin action on glucose clearance in skeletal muscle identically in aged and young subjects.