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Am J Physiol Endocrinol Metab (December 7, 2004). doi:10.1152/ajpendo.00477.2004
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Submitted on October 5, 2004
Accepted on December 1, 2004

Activation of p38 MAP Kinase Enhances Sensitivity of Muscle Glucose Transport to Insulin

Paige C. Geiger1, David C. Wright1, Dong-Ho Han1, and John O. Holloszy1*

1 Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

* To whom correspondence should be addressed. E-mail: jhollosz{at}im.wustl.edu.

Muscle contractile activity is followed by an increase in the sensitivity of glucose transport to insulin. There is evidence suggesting that activation of p38 MAP kinase (p38) is involved in the stimulation of glucose transport by insulin and contractions. Exercise results in an increase in p38 phosphorylation that last for hours. In this context, we tested the hypothesis that activation of p38 results in an increase in insulin sensitivity. Muscles were exposed to anisomycin for 30 min to activate p38. Anisomycin increased p38 phosphorylation ~2.5-fold and glucose transport activity 2 to 3-fold. Three hours after anisomycin treatment, by which the acute effect on glucose transport had partially worn off, sensitivity of muscle glucose transport to 60µU/ml insulin was markedly increased. Both the activation of p38 and the increase in insulin sensitivity induced by anisomycin were completely prevented by pretreatment of muscles with the p38 inhibitor SB202190. However, in contrast to the finding with anisomycin, inhibition of p38 activation did not prevent the contraction-induced increase in insulin sensitivity. Thus, our results show that activation of p38 is followed by an increase in insulin sensitivity of muscle glucose transport. However, activation of p38 is not necessary for induction of an increase in muscle insulin sensitivity by contractions. This finding provides evidence that contractions have an additional effect that makes p38 activation unnecessary for enhancement of insulin sensitivity by contractile activity.




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