Interleukin-6 Directly Increases Glucose Metabolism in Resting Human Skeletal Muscle

• Published in: Diabetes (New York, N.Y.) Vol. 56; no. 6; pp. 1630 - 1637
• Main Authors: Glund, Stephan, Deshmukh, Atul, Long, Yun Chau, Moller, Theodore, Koistinen, Heikki A, Caidahl, Kenneth, Zierath, Juleen R, Krook, Anna
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.06.2007
• Subjects: Adipocytes; Adult; Biological and medical sciences; Biological Transport - drug effects; Biopsy; Body fat; Clinical Medicine; Cytokines; Diabetes; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fundamental and applied biological sciences. Psychology; Genetic; Glucose; Glucose - metabolism; Glycogen - biosynthesis; Humans; Insulin resistance; Interleukin-6; Interleukin-6 - genetics; Interleukin-6 - pharmacology; Interleukin-6/genetics/pharmacology; Kinases; Klinisk medicin; Male; Medical sciences; Medicin och hälsovetenskap; Metabolism; Middle Aged; Muscle; Muscle, Skeletal - cytology; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; Obesity; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Plasma; Polymorphism; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Proteins; Reference Values; Restriction Fragment Length; Signal Transduction; Skeletal muscle; Skeletal/cytology/drug effects/metabolism; Striated muscle. Tendons; Tumor necrosis factor-TNF; Vertebrates: osteoarticular system, musculoskeletal system; United States; Endocrinopathy; Human; Interleukin 6; Diabetes mellitus; Cytokine; Glucose; Striated muscle; Metabolism
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db06-1733

Interleukin-6 Directly Increases Glucose Metabolism in Resting Human Skeletal Muscle Stephan Glund 1 , Atul Deshmukh 1 , Yun Chau Long 1 , Theodore Moller 1 , Heikki A. Koistinen 2 , Kenneth Caidahl 3 , Juleen R. Zierath 1 and Anna Krook 1 4 1 Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden 2 Helsinki University Central Hospital and Biomedicum, Helsinki, Finland 3 Department of Molecular Medicine and Surgery, Section for Clinical Physiology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden 4 Department of Physiology and Pharmacology, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden Address correspondence and reprint requests to Anna Krook, Department of Physiology and Pharmacology, Section for Integrative Physiology, Karolinska Institutet, von Eulers väg 4, SE-171 77 Stockholm, Sweden. E-mail: anna.krook{at}ki.se Abstract 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 GSK3α/β (glycogen synthase kinase 3α/β) 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. AMPK, AMP-activated protein kinase AS160, Akt substrate of 160 kDa GSK, glycogen synthase kinase IL, interleukin IRS, insulin receptor substrate KHBB, Krebs-Henseleit bicarbonate buffer MAPK, mitogen-activated protein kinase PKB, protein kinase B STAT, signal transducer and activator of transcription Footnotes Published ahead or print at http://diabetes.diabetesjournals.org on 15 March 2007. DOI: 10.2337/db06-1733. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted February 23, 2007. Received December 13, 2006. DIABETES