Exercise-induced increase in IL-6 level enhances GLUT4 expression and insulin sensitivity in mouse skeletal muscle

• Published in: Biochemical and biophysical research communications Vol. 473; no. 4; pp. 947 - 952
• Main Authors: Ikeda, Shin-ichi, Tamura, Yoshifumi, Kakehi, Saori, Sanada, Hiromi, Kawamori, Ryuzo, Watada, Hirotaka
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.05.2016
• Subjects: Animals; Cells, Cultured; Exercise; Glucose Transporter Type 4 - metabolism; GLUT4; Insulin - pharmacology; Insulin sensitivity; Interleukin-6; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - blood; Interleukin-6 - physiology; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal - drug effects; Muscle, Skeletal - enzymology; Muscle, Skeletal - metabolism; Physical Conditioning, Animal; Proto-Oncogene Proteins c-akt - metabolism; Exercise; GLUT4; Insulin sensitivity; Interleukin-6
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.03.159

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. •Exercise enhanced circulating IL-6, GLUT4 content and insulin sensitivity in muscle.•IL-6 neutralizing-antibody injection before exercise canceled all these effects.•IL-6 increased GLUT4 expression in muscle in vivo and in vitro.