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Diabetes. 2017 Mar;66(3):598-612. doi: 10.2337/db16-0530. Epub 2016 Oct 26.

Enhanced Muscle Insulin Sensitivity After Contraction/Exercise Is Mediated by AMPK.

Author information

1
Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
2
Section of Integrative Physiology, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
3
INSERM, U1016, Institut Cochin, Paris, France.
4
CNRS, UMR8104, Paris, France.
5
Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
6
Integrative Physiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
7
Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark jwojtaszewski@nexs.ku.dk.

Abstract

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.

PMID:
27797909
DOI:
10.2337/db16-0530
[Indexed for MEDLINE]
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