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Am J Physiol Endocrinol Metab 292: E1842-E1846, 2007. First published February 27, 2007; doi:10.1152/ajpendo.00701.2006
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IL-6 increases muscle insulin sensitivity only at superphysiological levels

Paige C. Geiger, Chad Hancock, David C. Wright, Dong-Ho Han, and John O. Holloszy

Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri

Submitted 20 December 2006 ; accepted in final form 21 February 2007

Exercise induces an increase in glucose transport in muscle. As the acute increase in glucose transport reverses, it is replaced by an increase in insulin sensitivity. Interleukin-6 (IL-6) increases with exercise and has been reported to activate AMP-activated protein kinase (AMPK). Based on this information, we hypothesized that IL-6 would result in an increase in muscle insulin sensitivity. Rat epitrochlearis and soleus muscles were incubated with 120 ng/ml IL-6. Exposure to IL-6 induced a modest acute increase in glucose transport and was followed 3.5 h later by an increase in insulin sensitivity in epitrochlearis but not soleus muscles. IL-6 also brought about an increase in AMPK phosphorylation in epitrochlearis muscles. We conclude that exposure of fast-twitch muscle to 120 ng/ml IL-6 increases insulin sensitivity by activating AMPK. However, exposure of epitrochlearis muscles to 10 ng/ml IL-6, a concentration >100-fold higher than that attained in plasma during exercise, had no effect on glucose transport or insulin sensitivity. These findings provide evidence that the increases in glucose transport and insulin sensitivity induced by IL-6 are pharmacological rather than physiological effects. We interpret our results as evidence that the increase in IL-6 during exercise does not play a role in the exercise-induced increases in muscle glucose uptake and insulin sensitivity.

adenosine 5'-triphosphate kinase; exercise; glucose transport; interleukin-6



Address for reprint requests and other correspondence: J. O. Holloszy, Washington Univ. School of Medicine, Applied Physiology, Campus Box 8113, 4566 Scott Ave., St. Louis, MO 63110 (e-mail: jhollosz{at}im.wustl.edu)




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