TITLE

Early and intermediate Amadori glycosylation adducts, oxidative stress, and endothelial dysfunction in the streptozotocin-induced diabetic rats vasculature Rodríguez-Mañas et al.: Endothelial dysfunction in diabetes

AUTHOR(S)
Rodríguez-Mañas, L.; Angulo, J.; Vallejo, S.; Peiró, C.; Sánchez-Ferrer, A.; Cercas, E.; López-Dóriga, P.; Sánchez-Ferrer, C. F.
PUB. DATE
April 2003
SOURCE
Diabetologia;Apr2003, Vol. 46 Issue 4, p556
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Aims/hypothesis. In a model of streptozotocin-induced Type 1 diabetes mellitus in rats of 9 weeks duration, we analysed time associations between the development of hyperglycaemia, early and intermediate glycosylation Amadori adducts, or AGE compared with enhancement of oxidative stress and endothelial dysfunction. Methods. Endothelial function was tested at several stages of streptozotocin-induced diabetes and after treatment with insulin, resulting in different concentrations of blood glucose, glycosylated haemoglobin (an Amadori adduct), and AGE. Other animals were studied antagonising the formation of AGE with aminoguanidine. Results. Relaxation in response to acetylcholine (1 nmol/l to 10 µmol/l) was tested in isolated segments from aorta or mesenteric microvessels. Impairment of endothelium-dependent relaxations occurred after 2 weeks of untreated diabetes. Preincubation of vessels affected with 100 U/ml superoxide dismutase improved the relaxations to acetylcholine, along the time-course of the endothelial impairment. This indicates the participation of reactive oxygen species on diabetic endothelial dysfunction. The impairment of endothelium-dependent relaxations was recovered after 3 more weeks of insulin treatment. Aminoguanidine treatment did not modify this pattern of development. The time course of the rise and disappearance of endothelial dysfunction showed a higher correlation with glycosylated haemoglobin concentrations than with blood glucose or serum AGE. Conclusion/interpretation. Enhancement of early and intermediate Amadori adducts of protein glycosylation was the factor showing a better relation with the development of endothelium impairment. These results are consistent with a role for these products in the development of diabetic vasculopathy.
ACCESSION #
16860867

 

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