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J Appl Physiol 94: 2337-2341, 2003. First published February 28, 2003; doi:10.1152/japplphysiol.00036.2003
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Vol. 94, Issue 6, 2337-2341, June 2003

Prior exercise increases basal and insulin-induced p38 mitogen-activated protein kinase phosphorylation in human skeletal muscle

Farah S. L. Thong1,*, Wim Derave2,*, Birgitte Ursø3, Bente Kiens4, and Erik A. Richter4

1 Programme in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8; 2 Department of Kinesiology, Faculty of Physical Education and Physiotherapy, Katholieke Universiteit Leuven, B-3001 Leuven, Belgium; 3 Diabetes Biology, Novo Nordisk, DK-2880 Bagsvaerd; and 4 Department of Human Physiology, Copenhagen Muscle Research Centre, Institute of Exercise and Sports Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark

We have examined the effects of insulin on p38 mitogen-activated protein kinase (MAPK) phosphorylation in human skeletal muscle and the effects of prior exercise hereon. Seven men performed 1-h one-legged knee extensor exercise 3 h before the initiation of a 100-min euglycemic-hyperinsulinemic (600 pmol/l) clamp. Glucose uptake across the legs was measured with the leg balance technique, and muscle biopsies were obtained from the rested and exercised vastus lateralis before and during insulin infusion. Net glucose uptake during the clamp was ~50% higher (P < 0.05) in the exercised leg than in the rested leg. Insulin induced a modest sustained 1.2- and 1.3-fold increase (P < 0.05) in p38 MAPK phosphorylation in the rested and exercised legs, respectively. However, p38 phosphorylation was ~50% higher (P < 0.05) in the exercised compared with the rested leg before and during insulin infusion. We conclude that a physiological concentration of insulin causes modest but sustained activation of the p38 MAPK pathway in human skeletal muscle. Furthermore, the stimulatory effect of exercise on p38 phosphorylation is persistent for at least 3 h after exercise and remains evident during subsequent insulin stimulation. Because p38 MAPK has been suggested to play a necessary role in activation of GLUT-4 at the cell surface, the present data may suggest a putative role of p38 MAPK in the increased insulin sensitivity of skeletal muscle after exercise.

glucose uptake; insulin sensitivity; stress-activated protein kinase; muscle glycogen

* F. S. L. Thong and W. Derave contributed equally to this work.




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