Interleukin-6 in combination with the interleukin-6 receptor stimulates glucose uptake in resting human skeletal muscle independently of insulin action.
OBJECTIVE
To examine if the physiological concentrations of both interleukin-6 (IL-6), in combination with IL-6 receptor (IL-6R), are able to stimulate glucose uptake in human skeletal muscle and to identify the associated signalling pathways.


METHODS
Skeletal muscle tissue (~60 mg) obtained from healthy female volunteers via muscle biopsy was subjected to incubation in the absence or presence of insulin (60 µU/ml), recombinant human IL-6 (rhIL-6) (4 ng/ml) or a combination of rhIL-6 (4 ng/ml) and rhIL-6R (100 ng/ml) for 30 min, with glucose transport measured for each incubation. Western blot analysis was conducted on key signalling proteins, protein kinase B (PKB/Akt), adenosine monophosphate kinase (AMPK) and mammalian target of rapamycin (mTOR) to gain an early insight into any differing transport mechanisms.


RESULTS
Human skeletal muscle exhibited increased glucose uptake with insulin (1.85-fold; p < 0.05) and stimulated phosphorylation of PKB/Akt and AMPK (0.98 ± 0.23 and 1.49 ± 0.13, respectively, phosphorylated: total; p < 0.05). IL-6/IL-6R increased phosphorylation of mTOR (fourfold, p < 0.05) compared to insulin, IL-6 alone and basal control. IL-6 did not stimulate glucose uptake but combined with IL-6R, induced 1.5-fold increase in glucose uptake (p < 0.05) and phosphorylation of AMPK (0.95 ± 0.19; phosphorylated: total, p < 0.05).


CONCLUSIONS
IL-6 in combination with IL-6R and not IL-6 alone increased glucose uptake in human skeletal muscle. IL-6/IL-6R-mediated glucose uptake occurred independently of PKB/Akt phosphorylation, showing that IL-6/IL-6R-induced glucose uptake is dependent on a divergent pathway.
School of Sport, Exercise & Health Sciences, Loughborough University, Loughborough, UK.
A
A
Saini
S H
SH
Faulkner
H
H
Moir
P
P
Warwick
J A
JA
King
M A
MA
Nimmo
D001692:Biological Transport; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D005947:Glucose
glucose uptake; human skeletal muscle; insulin; interleukin; interleukin-6 and receptor