Interleukin-6 Increases Insulin-Stimulated Glucose Disposal in Humans and Glucose Uptake and Fatty Acid Oxidation In Vitro via AMP-Activated Protein Kinase
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- Andrew L. Carey
- Cellular and Molecular Metabolism Laboratory, School of Medical Sciences, Royal Melbourne Institute of Technology (RMIT) University, Bundoora, Victoria, Australia
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- Gregory R. Steinberg
- St. Vincent’s Institute and Department of Medicine, The University of Melbourne, Fitzroy, Victoria, Australia
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- S. Lance Macaulay
- Commonwealth Scientific and Industrial Research Organization Molecular and Health Technologies, Parkville, Victoria, Australia
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- Walter G. Thomas
- Molecular Endocrinology Laboratory, Baker Heart Research Institute, Melbourne, Australia
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- Anna G. Holmes
- Cellular and Molecular Metabolism Laboratory, School of Medical Sciences, Royal Melbourne Institute of Technology (RMIT) University, Bundoora, Victoria, Australia
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- Georg Ramm
- Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
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- Oja Prelovsek
- Cellular and Molecular Metabolism Laboratory, School of Medical Sciences, Royal Melbourne Institute of Technology (RMIT) University, Bundoora, Victoria, Australia
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- Cordula Hohnen-Behrens
- Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
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- Matthew J. Watt
- Cellular and Molecular Metabolism Laboratory, School of Medical Sciences, Royal Melbourne Institute of Technology (RMIT) University, Bundoora, Victoria, Australia
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- David E. James
- Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
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- Bruce E. Kemp
- St. Vincent’s Institute and Department of Medicine, The University of Melbourne, Fitzroy, Victoria, Australia
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- Bente K. Pedersen
- The Centre for Inflammation and Metabolism, Department of Infectious Diseases and The Copenhagen Muscle Research Centre, Rigshospitalet University of Copenhagen, Faculty of Health Sciences, Copenhagen, Denmark
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- Mark A. Febbraio
- Cellular and Molecular Metabolism Laboratory, School of Medical Sciences, Royal Melbourne Institute of Technology (RMIT) University, Bundoora, Victoria, Australia
書誌事項
- 公開日
- 2006-10-01
- DOI
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- 10.2337/db05-1404
- 公開者
- American Diabetes Association
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説明
<jats:p>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 α-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.</jats:p>
収録刊行物
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- Diabetes
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Diabetes 55 (10), 2688-2697, 2006-10-01
American Diabetes Association
