Early reduction of circulating homocysteine levels in Goto-Kakizaki rat, a spontaneous nonobese model of type 2 diabetes - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Biochimica et Biophysica Acta - Molecular Basis of Disease Année : 2011

Early reduction of circulating homocysteine levels in Goto-Kakizaki rat, a spontaneous nonobese model of type 2 diabetes

Résumé

Diabetes mellitus is associated with increased risk for cardiovascular disorders, which are major causes of mortality in this disease. Hyperhomocysteinemia, defined by high plasma homocysteine levels, is an independent risk factor for the development of cardiovascular diseases. Type 2 diabetic patients have higher circulating homocysteine levels than healthy subjects and these levels are even higher in plasma of obese than nonobese diabetic patients. Homocysteine metabolism that has been studied in 2 animal models of type 2 diabetes with obesity, led to conflicting data. The aim of the present study was to analyze homocysteine metabolism in a spontaneous nonobese model of type 2 diabetes, the Goto-Kakizaki (GK) rats at various successive and well characterized stages of the disease: during early postnatal normoglycemia, at onset of hyperglycemia (around weaning), and during chronic mild hyperglycemia with progressive insulin resistance. Compared to age-matched Wistar controls, GK rats showed lower plasma levels of homocysteine and a falling trend in its major byproduct antioxidant, glutathione, from the prediabetic stage onwards. Concomitantly, GK rats exhibited increased liver activity of cystathionine beta synthase, which catalyzes the condensation of homocysteine with serine in the first step of the transsulfuration pathway. These results emphasize a strong association between homocysteine metabolism and insulin via the first step of the hepatic transsulfuration pathway in GK rats.
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Dates et versions

hal-00687789 , version 1 (15-04-2012)

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Christophe Noll, Gregory Lacraz, Jan Ehses, Josiane Coulaud, Danièle Bailbe, et al.. Early reduction of circulating homocysteine levels in Goto-Kakizaki rat, a spontaneous nonobese model of type 2 diabetes. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2011, 1812 (6), pp.699 - 702. ⟨10.1016/j.bbadis.2011.03.011⟩. ⟨hal-00687789⟩
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