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Diabetes 53:1643-1648, 2004
© 2004 by the American Diabetes Association, Inc.

Interleukin-6 Is a Novel Factor Mediating Glucose Homeostasis During Skeletal Muscle Contraction

Mark A. Febbraio1,2, Natalie Hiscock1,2,3, Massimo Sacchetti2, Christian P. Fischer2,3, and Bente K. Pedersen2,3

1 Skeletal Muscle Research Laboratory, Center for Nutrition Metabolism and Endocrinology, RMIT University, Bundoora, Australia
2 Copenhagen Muscle Research Centre, Copenhagen, Denmark
3 Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

The mechanisms that mediate the tightly controlled production and clearance of glucose during muscular work are unclear, and it has been suggested that an unidentified "work factor" exists that influences the contraction-induced increase in endogenous glucose production (EGP). The cytokine interleukin (IL)-6 is released from skeletal muscle during contraction. Here we show that IL-6 contributes to the contraction-induced increase in EGP. Six men performed 2 h of bicycle exercise on three separate occasions, at a relatively high intensity (HI) or at a low intensity with (LO + IL-6) or without (LO) an infusion of recombinant human IL-6 that matched the circulating concentration of IL-6 seen in HI exercise. The stable isotope 6,6 2H2 glucose was infused to calculate EGP (rate of glucose appearance [Ra]), whole-body glucose disposal (rate of glucose disappearance [Rd]), and metabolic clearance rate (MCR) of glucose. Glucose Ra, Rd, and MCR were higher (P < 0.05) at HI than at LO. Throughout exercise at LO + IL-6, glucose Ra and Rd were higher (P < 0.05) than LO, even though the exercise intensity was identical. In addition, MCR was higher (P < 0.05) at LO + IL-6 than at LO at 90 min. Insulin, glucagon, epinephrine, norepinephrine, cortisol, and growth hormone were identical when comparing LO + IL-6 with LO. These data suggest that IL-6 influences glucose homeostasis during exercise. Our results provide potential new insights into factors that mediate glucose production and disposal and implicates IL-6 in the so-called "work factor."

Address correspondence and reprint requests to Mark A. Febbraio, PhD, Associate Professor, Skeletal Muscle Research Laboratory, Center for Nutrition, Metabolism and Endocrinology, RMIT University, P.O. Box 71, Bundoora 3083, Victoria, Australia. E-mail: mark.febbraio{at}rmit.edu.au

Abbreviations: EGP, endogenous glucose production; FFA, free fatty acid; HI, high intensity; IL, interleukin; LO, low intensity; MCR, metabolic clearance rate; rh, recombinant human


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