Interleukin-6 acts as insulin sensitizer on glycogen synthesis in human skeletal muscle cells by phosphorylation of Ser473 of Akt.
Previous studies showed an insulin-"desensitizing" action of IL-6 on glycogen synthesis in hepatocytes. We recently found no inhibition of the proximal steps of the insulin signal cascade in human skeletal muscle cells. Because these data indicate a possible tissue-specific effect of IL-6, we investigated the influence of IL-6 on insulin-stimulated glycogen synthesis in these cells. At first, we found that incubation of the cells with 20 ng/ml IL-6 alone induced phosphorylation of Ser473 of Akt, but not of Thr308 time dependently and we observed that IL-6 augments insulin-induced Ser473 and Thr308 phosphorylation in the low nanomolar range of insulin. Moreover, IL-6 increased insulin-stimulated phosphorylation of glycogen synthase kinase-3. Accordingly, IL-6 enhanced glycogen synthesis in the presence of 3 and 10 nM insulin, whereas IL-6 alone had only a marginal effect. IL-6 treatment of C57Bl/6 mice readily stimulated phosphorylation of Ser473 in skeletal muscle. Our result that IL-6 did not induce Ser473 phosphorylation in the liver of these mice suggests a tissue-specific effect. Together, our data demonstrate a novel insulin-sensitizing function of IL-6 on glycogen synthesis in skeletal muscle cells and indicate that IL-6 exerts cell/tissue-specific effects on insulin action.
Weigert
Cora
C
Dept. of Internal Medicine, Div. of Endocrinology, Metabolism, Pathobiochemistry and Clinical Chemistry, Univ. of Tübingen, Otfried-Müller-Strasse 10, D-72076 Tübingen, Germany.
Hennige
Anita M
AM
Brodbeck
Katrin
K
Häring
Hans U
HU
Schleicher
Erwin D
ED
D000818:Animals; D002478:Cells, Cultured; D006003:Glycogen / Q000096:biosynthesis*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D022781:Hepatocytes / Q000201:enzymology; D007328:Insulin / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000201:enzymology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D007328:Insulin; D015850:Interleukin-6; D011518:Proto-Oncogene Proteins; D012694:Serine; D006003:Glycogen; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3