TY - JOUR
T1 - TNF-α levels are associated with skin capillary recruitment in humans
T2 - A potential explanation for the relationship between TNF-α and insulin resistance
AU - Ijzerman, Richard G.
AU - Voordouw, Jasper J.
AU - Van Weissenbruch, Mirjam M.
AU - Yudkin, John S.
AU - Serné, Erik H.
AU - Delemarre-Van De Waal, Henriette A.
AU - Stehouwer, Coen D.A.
PY - 2006/3/1
Y1 - 2006/3/1
N2 - The mechanism by which TNF-α (tumour necrosis factor-α) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-α has been suggested to cause defects in capillary function, with a decreased access of insulin and glucose to tissues. To test this hypothesis in humans, we assessed serum TNF-α concentrations, skin capillary recruitment and insulin sensitivity in a group of 37 healthy adults. In addition, we measured these variables in 21 of their prepubertal children. Serum TNF-α levels were measured by sandwich enzyme immunoassay, and insulin sensitivity was assessed with the hyperinsulinaemic euglycaemic clamp technique. Capillary recruitment during post-occlusive reactive hyperaemia was evaluated by videomicroscopy. In the adults, serum TNF-α levels were associated with both capillary recruitment (r = -0.40, P = 0.02) and insulin sensitivity (r = -0.33, P = 0.05). In addition, capillary recruitment was associated with insulin sensitivity (r = 0.34, P = 0.04). Regression analysis showed that the association between TNF-α and insulin sensitivity [-0.527 mg · kg-1 of body weight · min-1 per pmol/l per pg/ml TNF-α (95% confidence interval, -1.066 to 0.011); P = 0.05] decreased by 30% after adjustment for capillary recruitment. In the children, neither capillary recruitment (r = 0.33, P = 0.2) nor insulin sensitivity (r = -0.24, P = 0.4) was significantly associated with TNF-α. In conclusion, in adults, but not in children, serum TNF-α levels are associated with capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-α and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.
AB - The mechanism by which TNF-α (tumour necrosis factor-α) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-α has been suggested to cause defects in capillary function, with a decreased access of insulin and glucose to tissues. To test this hypothesis in humans, we assessed serum TNF-α concentrations, skin capillary recruitment and insulin sensitivity in a group of 37 healthy adults. In addition, we measured these variables in 21 of their prepubertal children. Serum TNF-α levels were measured by sandwich enzyme immunoassay, and insulin sensitivity was assessed with the hyperinsulinaemic euglycaemic clamp technique. Capillary recruitment during post-occlusive reactive hyperaemia was evaluated by videomicroscopy. In the adults, serum TNF-α levels were associated with both capillary recruitment (r = -0.40, P = 0.02) and insulin sensitivity (r = -0.33, P = 0.05). In addition, capillary recruitment was associated with insulin sensitivity (r = 0.34, P = 0.04). Regression analysis showed that the association between TNF-α and insulin sensitivity [-0.527 mg · kg-1 of body weight · min-1 per pmol/l per pg/ml TNF-α (95% confidence interval, -1.066 to 0.011); P = 0.05] decreased by 30% after adjustment for capillary recruitment. In the children, neither capillary recruitment (r = 0.33, P = 0.2) nor insulin sensitivity (r = -0.24, P = 0.4) was significantly associated with TNF-α. In conclusion, in adults, but not in children, serum TNF-α levels are associated with capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-α and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.
KW - Body mass index
KW - Capillary recruitment
KW - Insulin resistance
KW - Microcirculation
KW - Tumour necrosis factor (TNF)
UR - http://www.scopus.com/inward/record.url?scp=33644784745&partnerID=8YFLogxK
U2 - https://doi.org/10.1042/CS20050314
DO - https://doi.org/10.1042/CS20050314
M3 - Article
C2 - 16316318
SN - 0143-5221
VL - 110
SP - 361
EP - 368
JO - Clinical science
JF - Clinical science
IS - 3
ER -