Riassunto
Il diabete determina profonde alterazioni del metabolismo dei mucopolisaccaridi solforati, alterazioni che divengono evidenti ancor prima che si manifesti l'iperglicemia. Dopo 4 h dall'iniezione di solfato marcato, l'incorporazione di35S-solfato nei mucopolisaccaridi aortici di ratti diabetici appare aumentata; dopo tale periodo, la sintesi di composti solforati diminuisce. La concentrazione degli isomeri del condroitin-solfato nell'aorta aumenta nei ratti con diabete iniziale, diminuisce negli animali con diabete cronico. L'incorporazione di solfato marcato nel condroitin-solfato ad opera del sistema enzimatico presente nel fegato dei ratti diabetici è inibita da concentrazioni di enzima più elevate. Questa inibizione corrisponde ad una depressione nella formazione dell'intermedio trasportatore attivo di solfato, il fosfoadenosin-fosfosolfato, nel diabete. Tenendo conto di questi reperti e dei risultati ottenuti da altri ricercatori, viene proposta un'ipotesi relativa all'elevata incidenza, nel diabete, di malattie cardiovascolari.
Résumé
Le diabète provoque des profondes altérations du métabolisme des mucopolysaccharides sulfurés, altérations qui deviennent évidentes encore avant la manifestation de l'hyperglycémie. Quatre hrs après l'injection de sulfate marqué, on observe une augmentation de l'incorporation de35S-sulfate dans les mucopolysaccharides de l'aorte de rats diabétiques; par la suite, la synthèse de composés sulfurés baisse. La concentration des isomères du chondroitine-sulfate dans l'aorte augmente chez les rats attents de diabète initial, tandis qu'elle diminue chez les animaux avec diabète chronique. L'incorporation de sulfate marqué dans le chondroitine-sulfate par le système enzymatique qui se trouve dans le foie des rats diabétiques résulte inhibée par des concentrations plus hautes de l'enzyme. Cette inhibition correspond à une dépression de la formation ducarrier actif du sulfate, le phosphoadénosine-phosphosulfate, dans le diabète. À la lumière de ces données ainsi que des résultats obtenus d'autres auteurs, on avance une hypothèse concernant la haute incidence de maladies cardiovasculaires dans le diabète.
Resumen
La diabetes determina profundas alteraciones del metabolismo de los mucopolisacáridos sulfurados, alteraciones que se evidencian todavía antes de que se manifeste la hiperglicemia. Cuatro horas después de una inyección de sulfato marcado la incorporación de35S-sulfato en los mucopolisacáridos aórticos de ratas diabéticas se observa aumentada; transcurrido dicho período la síntesis de compuestos sulfurados disminuye. La concentración de los isómeros del condroitin-sulfato aumenta en las ratas con diabetes inicial y disminuye en los animales con diabetes crónica. La incorporación de sulfato marcado en el controitin-sulfato por obra del sistema enzímico presente en el hígado de las ratas diabéticas es inhibida por concentraciones de enzima más elevadas. Esa inhibición corresponde a una depresión en la formación de intermedio vector activo de sulfato, el fosfoadenosín-fosfosulfato, en la diabetes. Teniendo en cuenta estos resultados y los obtenidos por otros investigadores, se propone una hipótesis referente a la fuerte incidencia en la diabetes de enfermedades cardiovasculares.
Zusammenfassung
Diabetes führt zu tiefgreifenden Veränderungen im Metabolismus der schwefelsauren Mucopolysaccharide, welche sich schon vor der Hyperglykämie bemerkt machen. Die Inkorporation von35S-Sulfat in die Mucopolysaccharide der Aorta zuckerkranker Ratten ist 4 h nach der Injektion von markiertem Sulfat erhöht; danach nimmt die Synthese der schwefelsauren Verbindungen ab. Die Konzentration der Chondroitinsulfat-Isomere in der Aorta ist bei Ratten mit frischem Diabetes erhöht, nimmt aber bei den Tieren mit chronischem Diabetes ab. Die Inkorporation des markierten Schwefels in Chondroitinsulfat durch das Enzymsystem der Leber diabetischer Ratten wird durch erhöhte Enzymkonzentrationen gehemmt. Diese Hemmung entspricht einer Einschränkung der Bildung des aktiven Sulfat-Carriers, d.h. des Phosphoadenosin-Phosphosulfates bei Diabetes. Angesichts dieser Befunde und der Ergebnisse anderer Forscher wird eine Hypothese über die hohe Inzidenz von Herzkreislaufkrankheiten beim Diabetes mellitus formuliert.
Summary
Diabetes produces a profound alteration in the metabolism of sulfate mucopolysaccharides which becomes evident even before the development of hyperglycemia.35S-sulfate uptake into aortic mucopolysaccharides of diabetic rats is increased 4 hrs after injection of labeled sulfate, following which the synthesis of sulfated compounds is decreased. The concentration of aortic chondroitin sulfate isomers is increased in animals with early diabetes, whereas the concentration of these fractions is decreased in aortas of rats with chronic diabetes. The uptake of labeled sulfate into chondroitin sulfate by the hepatic enzyme system of diabetic rats is inhibited with higher concentrations of enzyme. This inhibition corresponds with a depression in the formation of the active sulfate carrier intermediate, phosphoadenosine-phosphosulfate, in diabetes. In view of these findings and results of other workers, a hypothesis is proposed concerning the high incidence of cardiovascular disease in diabetes.
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Supported by Grants Nos. 3493/68 and 3493 a) 69 from the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina. This work represents part of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the University of Buenos Aires.
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Cohen, M.P., Foglia, V.G. The effect of diabetes on the metabolism of mucopolysaccharides. Acta diabet. lat 8, 1079–1089 (1971). https://doi.org/10.1007/BF01550915
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DOI: https://doi.org/10.1007/BF01550915