1124 Exp Physiol 94.11 pp 1124–1131 Experimental Physiology – Research Paper Glucose ingestion during endurance training in men attenuates expression of myokine receptor Thorbjorn C. A. Akerstrom, Rikke Krogh-Madsen, Anne Marie Winther Petersen and Bente Klarlund Pedersen The Centre of Inflammation and Metabolism at Department of Infectious Diseases and Copenhagen Muscle Research Centre, Rigshospitalet and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark Glucose ingestion during exercise attenuates the release of the myokine interleukin-6 (IL-6) from working skeletal muscle, which results in a diminished increase in plasma IL-6. Interleukin-6 receptor α (IL-6Rα) expression in skeletal muscle is induced by acute exercise, mediated in part by an increased IL-6 concentration in the bloodstream. We hypothesized that endurance training would increase the density of IL-6Rα in skeletal muscle and that glucose ingestion would attenuate the effect. Nine subjects performed 10 weeks of one-legged knee-extensor training. They trained one leg (Glc-leg) while ingesting a glucose solution (Glc) and ingested a placebo (Plc) while training the other leg (Plc-leg). Endurance training increased peak power by ∼14% and reduced the exercise-induced gene expression of IL-6 and IL-6Rα in skeletal muscle and IL-6 plasma concentration. The IL-6Rα density increased to a lesser extent in the Glc-leg, suggesting that glucose ingestion attenuates the effect of training on IL-6Rα by blunting the IL-6 response. We conclude that glucose ingestion during endurance training attenuates the increase in IL-6Rα density. (Received 27 May 2009; accepted after revision 3 July 2009; first published online 10 July 2009) Corresponding author T. C. A. Akerstrom: The Centre of Inflammation and Metabolism and Copenhagen Muscle Research Centre, Section M7641, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. Email: thorbjorn akerstrom@inflammation-metabolism.dk Skeletal muscle is more than contractile machinery. Over the last decade, several studies have shown that muscle contraction initiates production and release of several different peptides in skeletal muscle, such as the cytokine interleukin-6 (IL-6; Steensberg et al. 2000, 2007; Penkowa et al. 2003; Keller et al. 2005b) and the CXC-family chemokine interleukin-8 (Nieman et al. 2001; Chan et al. 2004; Akerstrom et al. 2005). Collectively, these proteins have been termed myokines (Pedersen et al. 2007). Interleukin-6 was the first myokine to be identified and is also the myokine that has been studied most extensively (Fischer, 2006). Interleukin-6 is expressed in and released from contracting skeletal muscle during exercise, which can account for most of the increase in plasma IL-6 concentration observed during exercise (Steensberg et al. 2000). Interleukin-6 interacts specifically with IL-6 receptor α (IL-6Rα). Interleukin-6 receptor α lacks an intracellular signalling domain and forms a complex with the ubiquitous gp130 receptor to initiate intracellular signalling (Lutticken et al. 1994). Interleukin- 6 receptor α is expressed in skeletal muscle (Penkowa et al. 2003; Keller et al. 2005b), but what the specific role of the receptor might be is unclear. It is likely that IL-6 mediates possible effects on the muscle through IL-6Rα. It has been suggested that IL-6 is released from skeletal muscle during exercise to act in an endocrine manner, with effects on glucose (Febbraio et al. 2004) and fat metabolism (van Hall et al. 2003). Infusion of recombinant human IL-6 (rhIL-6) stimulates lipolysis and fat oxidation (van Hall et al. 2003) in humans at rest. However, the effect on glucose turnover is specific to exercise (Febbraio et al. 2004). Infusion of rhIL-6 at physiological concentrations during exercise increases glucose turnover (Febbraio et al. 2004), whereas rhIL-6 infusion has no effect on the rate of appearance or disappearance of glucose at rest (Steensberg et al. 2003), suggesting that there is a need for a cofactor or other condition present only during exercise for IL-6 to have an effect on glucose turnover. DOI: 10.1113/expphysiol.2009.048983 C  2009 The Authors. Journal compilation C  2009 The Physiological Society