Review

Exercise-stimulated glucose uptake — regulation and implications for glycaemic control

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AbstractAbstract

Skeletal muscle extracts glucose from the blood to maintain demand for carbohydrates as an energy source during exercise. Such uptake involves complex molecular signalling processes that are distinct from those activated by insulin. Exercise-stimulated glucose uptake is preserved in insulin-resistant muscle, emphasizing exercise as a therapeutic cornerstone among patients with metabolic diseases such as diabetes mellitus. Exercise increases uptake of glucose by up to 50-fold through the simultaneous stimulation of three key steps: delivery, transport across the muscle membrane and intracellular flux through metabolic processes (glycolysis and glucose oxidation). The available data suggest that no single signal transduction pathway can fully account for the regulation of any of these key steps, owing to redundancy in the signalling pathways that mediate glucose uptake to ensure maintenance of muscle energy supply during physical activity. Here, we review the molecular mechanisms that regulate the movement of glucose from the capillary bed into the muscle cell and discuss what is known about their integrated regulation during exercise. Novel developments within the field of mass spectrometry-based proteomics indicate that the known regulators of glucose uptake are only the tip of the iceberg. Consequently, many exciting discoveries clearly lie ahead.

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AcknowledgementsAcknowledgements

E.A.R is supported by grants from the Danish Council for Independent Research Natural Sciences (grant 4002-00492B), the Danish Council for Independent Research Medical Sciences (grant 0602-02273B), the Novo Nordisk Foundation (grant 1015429) and the University of Copenhagen Excellence Program for Interdisciplinary Research (“Physical activity and nutrition for improvement of health”). L.S. and M.K. are supported by Postdoctoral Fellowships from the Danish Council for Independent Research Medical Sciences (grants 5053–00155 and 4004–00233, respectively). T.E.J. is supported by an excellence grant from the Novo Nordisk Foundation (grant 15182).

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Affiliations

  1. Molecular Physiology Group, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.

    • Lykke Sylow
    • , Maximilian Kleinert
    • , Erik A. Richter
    •  & Thomas E. Jensen

  2. Institute for Diabetes and Obesity, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

    • Maximilian Kleinert

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Contributions

L.S., M.K., E.A.R. and T.E.J. researched the data for the article. L.S., M.K., E.A.R. and T.E.J. provided a substantial contribution to discussions of the content. L.S., M.K., E.A.R. and T.E.J. contributed equally to writing the article and to review and/or editing of the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

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Correspondence to Erik A. Richter.