Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro.
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-alpha 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.
Bastard
Jean-Philippe
JP
Service de Biochimie et Hormonologie, Hôpital Tenon-Rothschild, Assistance Publique-Hôpitaux de Paris (AP-HP), 75020 Paris, France. jean-philippe.bastard@tnn.ap-hop-paris.fr
Maachi
Mustapha
M
Van Nhieu
Jeanne Tran
JT
Jardel
Claude
C
Bruckert
Eric
E
Grimaldi
André
A
Robert
Jean-Jacques
JJ
Capeau
Jacqueline
J
Hainque
Bernard
B
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000378:metabolism*; D012016:Reference Values
D016207:Cytokines; D007328:Insulin; D015850:Interleukin-6; D005947:Glucose