Prolonged interleukin-6 administration enhances glucose tolerance and increases skeletal muscle PPAR alpha and UCP2 expression in rats

Holmes, A, Mesa, J, Neill, B, Chung, J, Carey, A, Steinberg, G, Kemp, B, Southgate, R, Lancaster, G, Clinton, B, Watt, M and Febbraio, M 2008, 'Prolonged interleukin-6 administration enhances glucose tolerance and increases skeletal muscle PPAR alpha and UCP2 expression in rats', Journal of Endocrinology, vol. 198, no. 2, pp. 367-374.


Document type: Journal Article
Collection: Journal Articles

Title Prolonged interleukin-6 administration enhances glucose tolerance and increases skeletal muscle PPAR alpha and UCP2 expression in rats
Author(s) Holmes, A
Mesa, J
Neill, B
Chung, J
Carey, A
Steinberg, G
Kemp, B
Southgate, R
Lancaster, G
Clinton, B
Watt, M
Febbraio, M
Year 2008
Journal name Journal of Endocrinology
Volume number 198
Issue number 2
Start page 367
End page 374
Total pages 8
Publisher Society for Endocrinology
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 14d 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 excised and rapidly frozen in liquid nitrogen for subsequent metabolic measures. Irrespective of the 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 i.p. 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 the 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.
Subject Exercise Physiology
Copyright notice © 2008 Society for Endocrinology
ISSN 0022-0795
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