The mechanism by which TNF-alpha (tumour necrosis factor-alpha) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-alpha 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-alpha 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-alpha 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-alpha 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-alpha and insulin sensitivity [-0.527 mg.kg(-1) of body weight.min(-1) per pmol/l per pg/ml TNF-alpha (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-alpha. In conclusion, in adults, but not in children, serum TNF-alpha levels are associated with capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-alpha and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.
Ijzerman, R. G., Voordouw, J. J., van Weissenbruch, M. M., Yudkin, J. S., Serne, E. H., van de Delemarre Waal, H. A., & Stehouwer, C. D. (2006). TNF-alpha levels are associated with skin capillary recruitment in humans: a potential explanation for the relationship between TNF-alpha and insulin resistance. Clinical Science, 110(3), 361-368. https://doi.org/10.1042/CS20050314