Exercise improves phosphatidylinositol-3,4,5-trisphosphate responsiveness of atypical protein kinase C and interacts with insulin signalling to peptide elongation in human skeletal muscle

Authors

  • Christian Frøsig,

    1. Copenhagen Muscle Research Centre, Section of  Human Physiology, Department of  Exercise and Sport Sciences, University of  Copenhagen, Copenhagen, Denmark
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  • Mini P. Sajan,

    1. James A. Haley Veterans Administration Hospital Research Service and Department of Internal Medicine, University of South Florida College of Medicine, Tampa Bay, FL, USA
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  • Stine J. Maarbjerg,

    1. Copenhagen Muscle Research Centre, Section of  Human Physiology, Department of  Exercise and Sport Sciences, University of  Copenhagen, Copenhagen, Denmark
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  • Nina Brandt,

    1. Copenhagen Muscle Research Centre, Section of  Human Physiology, Department of  Exercise and Sport Sciences, University of  Copenhagen, Copenhagen, Denmark
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  • Carsten Roepstorff,

    1. Copenhagen Muscle Research Centre, Section of  Human Physiology, Department of  Exercise and Sport Sciences, University of  Copenhagen, Copenhagen, Denmark
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  • Jørgen F. P. Wojtaszewski,

    1. Copenhagen Muscle Research Centre, Section of  Human Physiology, Department of  Exercise and Sport Sciences, University of  Copenhagen, Copenhagen, Denmark
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  • Bente Kiens,

    1. Copenhagen Muscle Research Centre, Section of  Human Physiology, Department of  Exercise and Sport Sciences, University of  Copenhagen, Copenhagen, Denmark
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  • Robert V. Farese,

    1. James A. Haley Veterans Administration Hospital Research Service and Department of Internal Medicine, University of South Florida College of Medicine, Tampa Bay, FL, USA
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  • Erik A. Richter

    1. Copenhagen Muscle Research Centre, Section of  Human Physiology, Department of  Exercise and Sport Sciences, University of  Copenhagen, Copenhagen, Denmark
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Corresponding author E. A. Richter: Copenhagen Muscle Research Centre, Section of Human Physiology, Department of Exercise and Sport Sciences, University of Copenhagen, 13, Universitetsparken, DK-2100, Copenhagen, Denmark. Email: erichter@ifi.ku.dk

Abstract

We investigated if acute endurance-type exercise interacts with insulin-stimulated activation of atypical protein kinase C (aPKC) and insulin signalling to peptide chain elongation in human skeletal muscle. Four hours after acute one-legged exercise, insulin-induced glucose uptake was ∼80% higher (N= 12, P < 0.05) in previously exercised muscle, measured during a euglycaemic–hyperinsulinaemic clamp (100 μU ml−1). Insulin increased (P < 0.05) both insulin receptor substrate (IRS)-1 and IRS-2 associated phosphatidylinositol (PI)-3 kinase activity and led to increased (P < 0.001) phosphorylation of Akt on Ser473 and Thr308 in skeletal muscle. Interestingly, in response to prior exercise IRS-2-associated PI-3 kinase activity was higher (P < 0.05) both at basal and during insulin stimulation. This coincided with correspondingly altered phosphorylation of the extracellular-regulated protein kinase 1/2 (ERK 1/2), p70S6 kinase (P70S6K), eukaryotic elongation factor 2 (eEF2) kinase and eEF2. aPKC was similarly activated by insulin in rested and exercised muscle, without detectable changes in aPKC Thr410 phosphorylation. However, when adding phosphatidylinositol-3,4,5-triphosphate (PIP3), the signalling product of PI-3 kinase, to basal muscle homogenates, aPKC was more potently activated (P= 0.01) in previously exercised muscle. Collectively, this study shows that endurance-type exercise interacts with insulin signalling to peptide chain elongation. Although protein turnover was not evaluated, this suggests that capacity for protein synthesis after acute endurance-type exercise may be improved. Furthermore, endurance exercise increased the responsiveness of aPKC to PIP3 providing a possible link to improved insulin-stimulated glucose uptake after exercise.

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