Enhanced muscle insulin sensitivity after contraction/exercise is mediated by AMPK

TY - JOUR

T1 - Enhanced muscle insulin sensitivity after contraction/exercise is mediated by AMPK

AU - Kjøbsted, Rasmus

AU - Munk-Hansen, Nanna

AU - Birk, Jesper Bratz

AU - Foretz, Marc

AU - Viollet, Benoit

AU - Björnholm, Marie

AU - Zierath, Juleen R

AU - Treebak, Jonas Thue

AU - Wojtaszewski, Jørgen

N1 - CURIS 2017 NEXS 073

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Earlier studies have demonstrated that muscle insulin sensitivity to stimulate glucose uptake is enhanced several hours after an acute bout of exercise. Using AICAR, we recently demonstrated that prior activation of AMPK is sufficient to increase insulin sensitivity in mouse skeletal muscle. Here we aimed to determine whether activation of AMPK is also a prerequisite for the ability of muscle contraction to increase insulin sensitivity. We found that prior in situ contraction of m. extensor digitorum longus (EDL) and treadmill exercise increased muscle and whole-body insulin sensitivity in wild-Type (WT) mice, respectively. These effects were not found in AMPKα1α2 muscle-specific knockout mice. Prior in situ contraction did not increase insulin sensitivity in m. soleus from either genotype. Improvement in muscle insulin sensitivity was not associated with enhanced glycogen synthase activity or proximal insulin signaling. However, in WT EDL muscle, prior in situ contraction enhanced insulin-stimulated phosphorylation of TBC1D4 Thr649 and Ser711. Such findings are also evident in prior exercised and insulin-sensitized human skeletal muscle. Collectively, our data suggest that the AMPK-TBC1D4 signaling axis is likely mediating the improved muscle insulin sensitivity after contraction/ exercise and illuminates an important and physiologically relevant role of AMPK in skeletal muscle.

AB - Earlier studies have demonstrated that muscle insulin sensitivity to stimulate glucose uptake is enhanced several hours after an acute bout of exercise. Using AICAR, we recently demonstrated that prior activation of AMPK is sufficient to increase insulin sensitivity in mouse skeletal muscle. Here we aimed to determine whether activation of AMPK is also a prerequisite for the ability of muscle contraction to increase insulin sensitivity. We found that prior in situ contraction of m. extensor digitorum longus (EDL) and treadmill exercise increased muscle and whole-body insulin sensitivity in wild-Type (WT) mice, respectively. These effects were not found in AMPKα1α2 muscle-specific knockout mice. Prior in situ contraction did not increase insulin sensitivity in m. soleus from either genotype. Improvement in muscle insulin sensitivity was not associated with enhanced glycogen synthase activity or proximal insulin signaling. However, in WT EDL muscle, prior in situ contraction enhanced insulin-stimulated phosphorylation of TBC1D4 Thr649 and Ser711. Such findings are also evident in prior exercised and insulin-sensitized human skeletal muscle. Collectively, our data suggest that the AMPK-TBC1D4 signaling axis is likely mediating the improved muscle insulin sensitivity after contraction/ exercise and illuminates an important and physiologically relevant role of AMPK in skeletal muscle.

KW - Faculty of Science

KW - Exercise

KW - Glucose uptake

KW - TBC1D4

KW - AS160

KW - AMP-activated protein kinase

U2 - 10.2337/db16-0530

DO - 10.2337/db16-0530

M3 - Journal article

C2 - 27797909

SN - 0012-1797

VL - 66

SP - 598

EP - 612

JO - Diabetes

JF - Diabetes

IS - 3

ER -