title: Exercise-induced increase in IL-6 level enhances GLUT4 expression and insulin sensitivity in mouse skeletal muscle.
abstract: A single bout of exercise is known to increase the insulin sensitivity of skeletal muscle; however, the underlying mechanism of this phenomenon is not fully understood. Because a single bout of exercise induces a transient increase in blood interleukin-6 (IL-6) level, we hypothesized that the enhancement of insulin sensitivity after a single bout of exercise in skeletal muscle is mediated at least in part through IL-6-dependent mechanisms. To test this hypothesis, C57BL6J mice were intravenously injected with normal IgG or an IL-6 neutralizing antibody before exercise. Twenty-four hours after a single bout of exercise, the plantaris muscle was harvested to measure insulin sensitivity and glucose transporter (GLUT)-4 expression levels by ex-vivo insulin-stimulated 2-deoxyglucose (2-DG) uptake and Western blotting, respectively. Compared with sedentary mice, mice that performed exercise showed enhanced IL-6 concentration, insulin-stimulated 2-DG uptake, and GLUT-4 expression in the plantaris muscle. The enhanced insulin sensitivity and GLUT4 expression were canceled by injection of the IL-6 neutralizing antibody before exercise. In addition, IL-6 injection increased GLUT4 expression, both in the plantaris muscle and the soleus muscle in C57BL6J mice. Furthermore, a short period of incubation with IL-6 increased GLUT4 expression in differentiated C2C12 myotubes. In summary, these results suggested that IL-6 increased GLUT4 expression in muscle and that this phenomenon may play a role in the post-exercise enhancement of insulin sensitivity in skeletal muscle.
authors.affiliation: Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Ikeda
authors.affiliation: Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: ys-tamur@juntendo.ac.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Kakehi
authors.affiliation: Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sanada
authors.affiliation: Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.affiliation: Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate School of Medicine, Tokyo, Japan; Center for Molecular Diabetology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D015850:Interleukin-6; D051057:Proto-Oncogene Proteins c-akt; D000093242:Interleukin-6 Inhibitors; C495694:Slc2a4 protein, rat
keywords: Exercise; GLUT4; Insulin sensitivity; Interleukin-6