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

Abstract

Key points A single bout of exercise is capable of increasing insulin sensitivity in human skeletal muscle. Whether this ability is affected by training status is not clear. Studies in mice suggest that the AMPK‐TBC1D4 signalling axis is important for the increased insulin‐stimulated glucose uptake after a single bout of exercise. The present study is the first longitudinal intervention study to show that, although exercise training increases insulin‐stimulated glucose uptake in skeletal muscle at rest, it diminishes the ability of a single bout of exercise to enhance muscle insulin‐stimulated glucose uptake. The present study provides novel data indicating that AMPK in human skeletal muscle is important for the insulin‐sensitizing effect of a single bout of exercise. Abstract 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 α2β2γ3 AMPK complex). Whether this is also the case in humans is unknown. Previous studies have shown that exercise training decreases the expression of the α2β2γ3 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 V̇O2 peak and expression of mitochondrial proteins in muscle, whereas the expression of AMPKγ3 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 α2β2γ3 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.

Regulation of Skeletal Muscle Glucose Transport and Glucose Metabolism by Exercise Training

“…Numerous studies have shown that aerobic exercise training increases hexokinase protein and activity levels ~25–100% in both human and rodent skeletal muscle [163,164,165,166,167,168,169,170,171,172]. In contrast, the effects of resistance exercise training on muscle hexokinase levels is less clear.…”

Epinephrine responsiveness is reduced in livers from trained mice

“…A single bout of exercise can have long-lasting metabolic effects (Richter, Mikines, Galbo, & Kiens, 1926;Steenberg et al, 2019;Sylow et al, 2019). Therefore, to determine if a single night of wheel running could affect liver responsiveness to epinephrine, the previous experiment was repeated, however, exercised mice (EX) ran on wheels for only one night (16:00-08:00 hr) instead of 12 days.…”

The Effects of a Single Versus Three Consecutive Sessions of Football Training on Postprandial Lipemia: a Randomized, Controlled Trial in Healthy, Recreationally Active Males

“…In a recent study, Steenberg et al [36] found that exercise training history diminishes the ability of a single bout of exercise to enhance insulin sensitivity, albeit not specifically pertaining to the postprandial response. Nonetheless, while our participants were not “trained” and had ceased any significant physical activity for 1 week before the initial trial, they did have experience playing football.…”

“…Nonetheless, while our participants were not “trained” and had ceased any significant physical activity for 1 week before the initial trial, they did have experience playing football. Steenberg et al [36] reported that exercise training increases insulin-stimulated glucose uptake of skeletal muscle at rest, but with no further gains in the acutely exercised leg. Thus, the elevated levels of glycogen in muscle after training might reduce the ability of acute exercise to enhance insulin-stimulated glucose uptake through an attenuation of activated protein kinase activity and may be applicable in our findings.…”