Suppressor of Cytokine Signaling 3 Expression and Insulin Resistance in Skeletal Muscle of Obese and Type 2 Diabetic Patients

  1. Jennifer Rieusset1,
  2. Karim Bouzakri1,
  3. Emmanuel Chevillotte1,
  4. Nadège Ricard1,
  5. Delphine Jacquet2,
  6. Jean-Philippe Bastard3,
  7. Martine Laville14 and
  8. Hubert Vidal14
  1. 1INSERM U449/INRA U1235 and Centre de Recherche en Nutrition Humaine de Lyon, IFR 62, Faculté de Médecine René Laennec, Université Claude Bernard Lyon-1, Lyon, France
  2. 2INSERM U457, Hôpital Robert Debré, Paris, France
  3. 3Service de Biochimie et Hormonologie, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris and INSERM U402, Paris, France
  4. 4Service d’Endocrinologie, Diabétologie et Nutrition, Hôpital Edouard Herriot, Lyon, France
  1. Address correspondence and reprint requests to Dr. Jennifer Rieusset, INSERM U449/INRA U1235, Faculté de Médecine René Laennec, Rue G. Paradin, F-69372 Lyon, Cedex 08, France. E-mail: jennifer.rieusset{at}univ-lyon1.fr

Abstract

Interleukin-6 (IL-6) could be a possible mediator of insulin resistance. We investigated whether IL-6 could inhibit insulin signaling in human skeletal myotubes and whether suppressor of cytokine signaling 3 (SOCS-3) could be related to insulin resistance in vivo in humans. IL-6 inhibited insulin signaling and induced SOCS-3 expression in differentiated myotubes. SOCS-3 mRNA levels were significantly increased in the skeletal muscle of type 2 diabetic patients compared with control subjects and correlated with reduced insulin-stimulated glucose uptake. In contrast, SOCS-3 mRNA levels were reduced in muscle of obese nondiabetic subjects compared with type 2 diabetic patients, despite similar circulating concentrations of IL-6. Increased SOCS-3 mRNA levels in diabetes were not attributable to hyperglycemia, as type 1 diabetic patients had normal SOCS-3 mRNA expression in muscle. However, the combination of high glucose and IL-6 levels in type 2 diabetic patients may induce SOCS-3 expression, as has been seen in human muscle cells. In subcutaneous adipose tissue, SOCS-3 mRNA levels were increased in obese individuals and strongly correlated with IL-6 expression, supporting a paracrine effect of IL-6 on SOCS-3 expression in fat. Taken together, our results showed that SOCS-3 expression in human skeletal muscle in vivo is not related to insulin resistance in the presence of elevated IL-6 concentrations and suggest that cytokine action could differ in type 2 diabetic patients and nondiabetic obese subjects.

Footnotes

    • Accepted May 28, 2004.
    • Received January 20, 2004.
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