|
 |
|
|||||||
|
|||||||||
Diabetes 53:2232-2241, 2004
© 2004 by the American Diabetes Association, Inc.
Suppressor of Cytokine Signaling 3 Expression and Insulin Resistance in Skeletal Muscle of Obese and Type 2 Diabetic Patients
1 INSERM 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 INSERM U457, Hôpital Robert Debré, Paris, France
3 Service de Biochimie et Hormonologie, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris and INSERM U402, Paris, France
4 Service d’Endocrinologie, Diabétologie et Nutrition, Hôpital Edouard Herriot, Lyon, France
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.
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
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Qatanani and M. A. Lazar Mechanisms of obesity-associated insulin resistance: many choices on the menu Genes & Dev., June 15, 2007; 21(12): 1443 - 1455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Ronn, N. Billestrup, and T. Mandrup-Poulsen Diabetes and Suppressors of Cytokine Signaling Proteins Diabetes, February 1, 2007; 56(2): 541 - 548. [Full Text] [PDF]
|
|
|
|
|
|
Y. W. Asmann, C. S. Stump, K. R. Short, J. M. Coenen-Schimke, Z. Guo, M. L. Bigelow, and K. S. Nair Skeletal Muscle Mitochondrial Functions, Mitochondrial DNA Copy Numbers, and Gene Transcript Profiles in Type 2 Diabetic and Nondiabetic Subjects at Equal Levels of Low or High Insulin and Euglycemia Diabetes, December 1, 2006; 55(12): 3309 - 3319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. ALEXANDRAKI, C. PIPERI, C. KALOFOUTIS, J. SINGH, A. ALAVERAS, and A. KALOFOUTIS Inflammatory Process in Type 2 Diabetes: The Role of Cytokines Ann. N.Y. Acad. Sci., November 1, 2006; 1084(1): 89 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. O. L. Jorgensen, N. Jessen, S. B. Pedersen, E. Vestergaard, L. Gormsen, S. A. Lund, and N. Billestrup GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus Am J Physiol Endocrinol Metab, November 1, 2006; 291(5): E899 - E905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Steinberg, A. J. McAinch, M. B. Chen, P. E. O'Brien, J. B. Dixon, D. Cameron-Smith, and B. E. Kemp The Suppressor of Cytokine Signaling 3 Inhibits Leptin Activation of AMP-Kinase in Cultured Skeletal Muscle of Obese Humans J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3592 - 3597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Spangenburg, D. A. Brown, M. S. Johnson, and R. L. Moore Exercise increases SOCS-3 expression in rat skeletal muscle: potential relationship to IL-6 expression J. Physiol., May 1, 2006; 572(3): 839 - 848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. P. Kristiansen and T. Mandrup-Poulsen Interleukin-6 and Diabetes: The Good, the Bad, or the Indifferent? Diabetes, December 1, 2005; 54(suppl_2): S114 - S124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Bach, D. Naon, S. Pich, F. X. Soriano, N. Vega, J. Rieusset, M. Laville, C. Guillet, Y. Boirie, H. Wallberg-Henriksson, et al. Expression of Mfn2, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle: Effects of Type 2 Diabetes, Obesity, Weight Loss, and the Regulatory Role of Tumor Necrosis Factor {alpha} and Interleukin-6 Diabetes, September 1, 2005; 54(9): 2685 - 2693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Klover, A. H. Clementi, and R. A. Mooney Interleukin-6 Depletion Selectively Improves Hepatic Insulin Action in Obesity Endocrinology, August 1, 2005; 146(8): 3417 - 3427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Weigert, A. M. Hennige, K. Brodbeck, H. U. Haring, and E. D. Schleicher Interleukin-6 acts as insulin sensitizer on glycogen synthesis in human skeletal muscle cells by phosphorylation of Ser473 of Akt Am J Physiol Endocrinol Metab, August 1, 2005; 289(2): E251 - E257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Yu and H. N. Ginsberg Adipocyte Signaling and Lipid Homeostasis: Sequelae of Insulin-Resistant Adipose Tissue Circ. Res., May 27, 2005; 96(10): 1042 - 1052. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |