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Adipose Tissue IL-6 Content Correlates with Resistance to Insulin Activation of Glucose Uptake both in Vivo and in Vitro

Service de Biochimie et Hormonologie (J.-P.B., M.M., J.C.), Hôpital Tenon-Rothschild, Assistance Publique-Hôpitaux de Paris (AP-HP), 75020 Paris; INSERM U-402, Faculté de Médecine Saint-Antoine (J.-P.B., J.C.), Université Paris VI, 75012 Paris; Département de Pathologie (J.T.V.N.), Hôpital Henri Mondor, AP-HP et Université Paris XII, 94000 Créteil; Service de Biochimie (C.J., B.H.), Hôpital de la Salpêtrière, AP-HP, 75013 Paris; Service d’Endocrinologie et Métabolisme (E.B.), Hôpital de la Pitié, AP-HP, Paris; Service de Diabétologie et Métabolisme (A.G.), Hôpital de la Pitié, AP-HP, 75013 Paris; and Fédération de Pédiatrie (J.-J.R.), Diabète de l’Enfant et de l’Adolescent, Hôpital Necker-Enfants Malades, AP-HP, 75015 Paris, France

Address all correspondence and requests for reprints to: Dr. Jean-Philippe Bastard, M.D., Ph.D., Service de Biochimie et Hormonologie, Hôpital Tenon, 4 rue de la Chine, 75970, Paris Cedex 20, France. E-mail: . jean-philippe.bastard{at}tnn.ap-hop-paris.fr

Abstract

Obesity and type 2 diabetes are associated with insulin resistance, the mechanisms of which remain poorly understood. A significant correlation between circulating IL-6 level and insulin sensitivity has recently been found in humans. Because adipose tissue could be a significant source of IL-6, we analyzed the relationship between the levels of adipose tissue IL-6 and insulin action in vivo, during a hyperinsulinemic normoglycemic clamp, and in vitro by measuring glucose transport in adipocytes from 12 obese subjects with (n = 7) or without (n = 5) diabetes. We observed an inverse correlation between adipose tissue IL-6 content and maximal insulin-responsiveness measured in vivo (P < 0.02) and in vitro (P < 0.02). Conversely, there was no significant correlation between these two later parameters and adipose tissue leptin or tumor necrosis factor- protein contents. Furthermore, we showed, for the first time, the presence of immunoreactive IL-6 receptors in the plasma membrane of human abdominal sc adipocytes. This suggests that locally secreted IL-6 could act on adipocytes by an autocrine/paracrine mechanism. In conclusion, increased IL-6 production by sc adipose cells might participate to the insulin-resistant state observed in human obesity.

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