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.
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March 2006
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Research Article|
February 10 2006
TNF-α levels are associated with skin capillary recruitment in humans: a potential explanation for the relationship between TNF-α and insulin resistance
Richard G. Ijzerman;
Richard G. Ijzerman
1
*Department of Internal Medicine, Institute for Cardiovascular Research-Vrije Universiteit, VU University Medical Center, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands
†Department of Paediatrics, Institute for Endocrinology, Reproduction and Metabolism, VU University Medical Center, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands
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Jasper J. Voordouw;
Jasper J. Voordouw
1
*Department of Internal Medicine, Institute for Cardiovascular Research-Vrije Universiteit, VU University Medical Center, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands
†Department of Paediatrics, Institute for Endocrinology, Reproduction and Metabolism, VU University Medical Center, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands
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Mirjam M. Van Weissenbruch;
Mirjam M. Van Weissenbruch
†Department of Paediatrics, Institute for Endocrinology, Reproduction and Metabolism, VU University Medical Center, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands
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John S. Yudkin;
John S. Yudkin
‡Department of Medicine, University College London Medical School, Whittington Hospital, Highgate Hill, London N19 5LW, U.K.
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Erik H. Serné;
Erik H. Serné
*Department of Internal Medicine, Institute for Cardiovascular Research-Vrije Universiteit, VU University Medical Center, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands
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Henriette A. Delemarre-Van De Waal;
Henriette A. Delemarre-Van De Waal
†Department of Paediatrics, Institute for Endocrinology, Reproduction and Metabolism, VU University Medical Center, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands
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Coen D. A. Stehouwer
§Department of Internal Medicine, Academic Hospital Maastricht, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands
Correspondence: Professor Coen D. A. Stehouwer (email csteh@sint.azm.nl).
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Clin Sci (Lond) (2006) 110 (3): 361–368.
Article history
Received:
October 17 2005
Accepted:
November 29 2005
Accepted Manuscript online:
November 29 2005
Citation
Richard G. Ijzerman, Jasper J. Voordouw, Mirjam M. Van Weissenbruch, John S. Yudkin, Erik H. Serné, Henriette A. Delemarre-Van De Waal, Coen D. A. Stehouwer; TNF-α levels are associated with skin capillary recruitment in humans: a potential explanation for the relationship between TNF-α and insulin resistance. Clin Sci (Lond) 1 March 2006; 110 (3): 361–368. doi: https://doi.org/10.1042/CS20050314
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