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Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase


Although interleukin-6 (IL-6) has been associated with insulin resistance, little is known regarding the effects of IL-6 on insulin sensitivity in humans in vivo. Here, we show that IL-6 infusion increases glucose disposal without affecting the complete suppression of endogenous glucose production during a hyperinsulinemic-euglycemic clamp in healthy humans. Because skeletal muscle accounts for most of the insulin-stimulated glucose disposal in vivo, we examined the mechanism(s) by which IL-6 may affect muscle metabolism using L6 myotubes. IL-6 treatment increased fatty acid oxidation, basal and insulin-stimulated glucose uptake, and translocation of GLUT4 to the plasma membrane. Furthermore, IL-6 rapidly and markedly increased AMP-activated protein kinase (AMPK). To determine whether the activation of AMPK mediated cellular metabolic events, we conducted experiments using L6 myotubes infected with dominant-negative AMPK alpha-subunit. The effects described above were abrogated in AMPK dominant-negative-infected cells. Our results demonstrate that acute IL-6 treatment enhances insulin-stimulated glucose disposal in humans in vivo, while the effects of IL-6 on glucose and fatty acid metabolism in vitro appear to be mediated by AMPK.

Type Journal
ISBN 0012-1797 (Print)
Authors Carey, A. L.;Steinberg, G. R.;Macaulay, S. L.;Thomas, W. G.;Holmes, A. G.;Ramm, G.;Prelovsek, O.;Hohnen-Behrens, C.;Watt, M. J.;James, D. E.;Kemp, B. E.;Pedersen, B. K.;Febbraio, M. A. :
Publisher Name DIABETES
Published Date 2006-01-01
Published Volume 55
Published Issue 10
Published Pages 2688-97
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version