Exercise training reduces the insulin-sensitizing effect of acute exercise in human skeletal muscle

TY - JOUR

T1 - Exercise training reduces the insulin-sensitizing effect of acute exercise in human skeletal muscle

AU - Steenberg, Dorte Enggaard

AU - Jørgensen, Nichlas B

AU - Birk, Jesper Bratz

AU - Sjøberg, Kim Anker

AU - Kiens, Bente

AU - Richter, Erik

AU - Wojtaszewski, Jørgen

N1 - CURIS 2019 NEXS 012

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 α 2 β 2 γ 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 α 2 β 2 γ 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 O2peak 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 α 2 β 2 γ 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.

AB - 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 α 2 β 2 γ 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 α 2 β 2 γ 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 O2peak 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 α 2 β 2 γ 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.

KW - Faculty of Science

KW - AMP-activated protein kinase

KW - TBC1D4

KW - Glucose uptake

U2 - 10.1113/jp276735

DO - 10.1113/jp276735

M3 - Journal article

C2 - 30325018

SN - 0022-3751

VL - 597

SP - 89

EP - 103

JO - The Journal of Physiology

JF - The Journal of Physiology

IS - 1

ER -