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Diabetic ketosis activates lymphomonocyte‐inducible nitric oxide synthase
Author(s) -
Iori E.,
Calò L.,
Valbusa D.,
Ceolotto G.,
Milani M.,
Pengo V.,
De Kreutzenberg S. V.,
Tiengo A.,
Avogaro A.
Publication year - 2002
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1046/j.1464-5491.2002.00787.x
Subject(s) - endocrinology , medicine , ketosis , nitric oxide synthase , thrombomodulin , nitric oxide , proinflammatory cytokine , diabetes mellitus , inflammation , platelet , thrombin
Aims Inappropriate production of nitric oxide (NO) may be responsible for the haemodynamic disturbances of diabetic ketoacidosis. We investigated whether this metabolic condition is associated with increased plasma nitrate (the stable oxidation product of NO) levels and NO synthase gene expression in lymphomonocytes. Research design and methods Plasma nitrate concentrations, lymphomonocyte‐inducible nitric oxide synthase (iNOS) gene expression, tumour necrosis factor‐alpha (TNF‐α) and soluble thrombomodulin were measured in 11 Type 1 diabetic patients at baseline, during mild ketosis and after euglycaemia was re‐established. Results During diabetic ketosis plasma nitrate concentrations were higher (18 (16–21) vs. 9 (7–11) µmol/l; (95% lower‐upper confidence interval) P < 0.05) than at baseline. At baseline lymphomonocyte iNOS mRNA expression and iNOS protein levels were undetectable, but in ketosis both were increased (both at P < 0.0001). After recovery from ketosis, NO 3 concentration, iNOS mRNA, and iNOS expression (270 ± 36%, mean ± sd ) decreased but not significantly. No significant changes were observed in either TNF‐α or soluble thrombomodulin levels between the three conditions. Conclusions Diabetic ketosis is associated with increased nitrate levels and the activation of iNOS expression in circulating lymphomonocytes, but it does not affect either the proinflammatory cytokine TNF‐α or a marker of endothelial dysfunction such as thrombomodulin. Our data support the hypothesis that, during diabetic ketosis, alterations in NO homeostasis are present in circulating lymphomonocytes.