Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle.
Interleukin (IL)-6 is a proinflammatory cytokine shown to modify insulin sensitivity. Elevated plasma levels of IL-6 are observed in insulin-resistant states. Interestingly, plasma IL-6 levels also increase during exercise, with skeletal muscle being the predominant source. Thus, IL-6 has also been suggested to promote insulin-mediated glucose utilization. In this study, we determined the direct effects of IL-6 on glucose transport and signal transduction in human skeletal muscle. Skeletal muscle strips were prepared from vastus lateralis biopsies obtained from 22 healthy men. Muscle strips were incubated with or without IL-6 (120 ng/ml). We found that IL-6 increased glucose transport in human skeletal muscle 1.3-fold (P < 0.05). A 30-min pre-exposure to IL-6 did not affect insulin-stimulated glucose transport. IL-6 also increased skeletal muscle glucose incorporation into glycogen, as well as glucose oxidation (1.5- and 1.3-fold, respectively; P < 0.05). IL-6 increased phosphorylation of STAT3 (signal transducer and activator of transcription 3; P < 0.05), AMP-activated protein kinase (P = 0.063), and p38 mitogen-activated protein kinase (P < 0.05) and reduced phosphorylation of S6 ribosomal protein (P < 0.05). In contrast, phosphorylation of protein kinase B/Akt, AS160 (Akt substrate of 160 kDa), and GSK3alpha/beta (glycogen synthase kinase 3alpha/beta) as well as insulin receptor substrate 1-associated phosphatidylinositol 3-kinase activity remained unaltered. In conclusion, acute IL-6 exposure increases glucose metabolism in resting human skeletal muscle. Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure.
Glund
Stephan
S
Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Deshmukh
Atul
A
Long
Yun Chau
YC
Moller
Theodore
T
Koistinen
Heikki A
HA
Caidahl
Kenneth
K
Zierath
Juleen R
JR
Krook
Anna
A
D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D001706:Biopsy; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012016:Reference Values; D015398:Signal Transduction
D015850:Interleukin-6; D006003:Glycogen; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose