Interleukin-6 in combination with the interleukin-6 receptor stimulates glucose uptake in resting human skeletal muscle independently of insulin action

Research output: Contribution to journalArticlepeer-review


  • A. Saini
  • S. H. Faulkner
  • H. Moir
  • P. Warwick
  • J. A. King

Colleges, School and Institutes

External organisations

  • Loughborough University
  • Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Department of Physiology and Pharmacology, Molecular Exercise Physiology Research Group, Karolinska Institutet
  • Faculty of Science, Engineering and Computing, Penrhyn Road, Kingston upon Thames


AIM: 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.

Bibliographic note

© 2014 John Wiley & Sons Ltd.


Original languageEnglish
Pages (from-to)931-6
Number of pages6
JournalDiabetes, Obesity and Metabolism
Issue number10
Early online date7 Apr 2014
Publication statusPublished - Oct 2014


  • Glucose uptake, Human skeletal muscle, Insulin, Interleukin, Interleukin-6 and receptor