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A Holmes, Cellular and Molecular metabolism Laboratory, Diabetes & Metabolism Division, Baker Heart Research Institute, Melbourne, Australia
J Mesa, Cellular and Molecular metabolism Laboratory, Diabetes & Metabolism Division, Baker Heart Research Institute, Melbourne, Australia
B Neill, Cellular and Molecular metabolism Laboratory, Diabetes & Metabolism Division, Baker Heart Research Institute, Melbourne, Australia
J Chung, Cellular and Molecular metabolism Laboratory, Diabetes & Metabolism Division, Baker Heart Research Institute, Melbourne, Australia
A Carey, School of Medical Sciences, RMIT University, Bundoora, Australia
G Steinberg, St Vincent's Institute and Department of Medicine, University of Melbourne, Melbourne, Australia
B Kemp, St Vincent's Institute and Department of Medicine, University of Melbourne, Melbourne, Australia
R Southgate, Cellular and Molecular metabolism Laboratory, Diabetes & Metabolism Division, Baker Heart Research Institute, Melbourne, Australia
G Lancaster, Cellular and Molecular metabolism Laboratory, Diabetes & Metabolism Division, Baker Heart Research Institute, Melbourne, Australia
C Bruce, Cellular and Molecular metabolism Laboratory, Diabetes & Metabolism Division, Baker Heart Research Institute, Melbourne, Australia
M Watt, Department of Physiology,, Monash University, Clayton, Australia
M Febbraio, Cellular and Molecular metabolism Laboratory, Diabetes & Metabolism Division, Baker Heart Research Institute, Melbourne, Australia

Correspondence: Mark Febbraio, Email: mark.febbraio{at}baker.edu.au

Abstract

Chronic elevations in interleukin (IL)-6 have been associated with insulin resistance, but acute IL-6 administration can enhance insulin sensitivity. Our aim was to exogenously administer IL-6 to rats to elicit either chronic or repeated acute elevations in systemic IL-6. We hypothesized that a continuous elevation of IL-6 would inhibit glucose tolerance and insulin sensitivity while acute intermittent elevations would improve it. Male Wistar rats were treated for 14 d with recombinant human IL-6 (2.4 µg/day) or saline administered either by miniosmotic pump (Continuous IL-6) or via twice daily injection (Intermittent IL-6). Glucose and insulin tolerance tests were performed following 14 d treatment and 24 h later rats were administered a bolus of insulin (150 mU/g) or saline intraperitoneally. Approximately 10 min after insulin injection soleus, gastrocnemius and liver were excized and rapidly frozen in liquid nitrogen for subsequent metabolic measures. Irrespective of mode of delivery, IL-6 treatment increased basal insulin sensitivity, as measured by the homeostatic model assessment of insulin resistance, and enhanced glucose clearance during an intraperitoneal glucose tolerance test. IL-6 increased circulating fatty acids, but did not increase triglyceride accumulation in either skeletal muscle or liver, while it increased the protein expression of both PPAR and UCP2 in skeletal muscle, suggesting that IL-6 can enhance fat oxidation via mitochondrial uncoupling. These data demonstrate that, irrespective of mode of delivery, IL-6 administration over 2 weeks enhances glucose tolerance. Our results do not support the notion that prolonged chronically elevated IL-6 impairs insulin action in vivo.

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				S. R. Gray, A. Ratkevicius, H. Wackerhage, P. Coats, and M. A. Nimmo The effect of interleukin-6 and the interleukin-6 receptor on glucose transport in mouse skeletal muscle Exp Physiol, August 1, 2009; 94(8): 899 - 905. [Abstract] [Full Text] [PDF]