Exercise training reduces the insulin-sensitizing effect of a single bout of exercise in human skeletal muscle

Not only chronic exercise training, but also a single bout of exercise, increases insulin-stimulated glucose uptake in skeletal muscle. However, it is not well described how adaptations to exercise training affect the ability of a single bout of exercise to increase insulin sensitivity. Rodent studies suggest that the insulin-sensitizing effect of a single bout of exercise is AMPK-dependent (presumably via the alpha(2)beta(2)gamma(3) AMPK complex). Whether this is also the case in humans is unknown. Previous studies have shown that exercise training decreases the expression of the alpha(2)beta(2)gamma(3) AMPK complex and diminishes the activation of this complex during exercise. Thus, we hypothesized that exercise training diminishes the ability of a single bout of exercise to enhance muscle insulin sensitivity. We investigated nine healthy male subjects who performed one-legged knee-extensor exercise at the same relative intensity before and after 12 weeks of exercise training. Training increased (V) over dot(O2 peak) and expression of mitochondrial proteins in muscle, whereas the expression of AMPK gamma 3 was decreased. Training also increased whole body and muscle insulin sensitivity. Interestingly, insulin-stimulated glucose uptake in the acutely exercised leg was not enhanced further by training. Thus, the increase in insulin-stimulated glucose uptake following a single bout of one-legged exercise was lower in the trained vs. untrained state. This was associated with reduced signalling via confirmed alpha(2)beta(2)gamma(3) AMPK downstream targets (ACC and TBC1D4). These results suggest that the insulin-sensitizing effect of a single bout of exercise is also AMPK-dependent in human skeletal muscle.