Prolonged interleukin-6 administration enhances glucose tolerance and increases skeletal muscle PPARalpha and UCP2 expression in rats.
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 microy) 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 PPARalpha 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.
Holmes
Anna G
AG
Diabetes and Metabolism Division, Cellular and Molecular Metabolism Laboratory, Baker Heart Research Institute, PO Box 6492, St Kilda Road Central, Melbourne, Victoria 8008, Australia.
Mesa
Jose L
JL
Neill
Bronwyn A
BA
Chung
Jason
J
Carey
Andrew L
AL
Steinberg
Gregory R
GR
Kemp
Bruce E
BE
Southgate
Robert J
RJ
Lancaster
Graeme I
GI
Bruce
Clinton R
CR
Watt
Matthew J
MJ
Febbraio
Mark A
MA
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D005951:Glucose Tolerance Test; D015151:Immunoblotting; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D001786:Blood Glucose; D015850:Interleukin-6; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047493:PPAR alpha; C000604389:UCP2 protein, human; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D055372:AMP-Activated Protein Kinases