title: Early reduction of circulating homocysteine levels in Goto-Kakizaki rat, a spontaneous nonobese model of type 2 diabetes.
abstract: 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 rats at various successive and well characterized stages of the disease: during early postnatal normoglycemia, at the onset of hyperglycemia (around weaning), and during chronic mild hyperglycemia with progressive insulin resistance. Compared to age-matched Wistar controls, Goto-Kakizaki rats showed lower plasma levels of homocysteine and a falling trend in its major byproduct antioxidant, glutathione, from the prediabetic stage onwards. Concomitantly, Goto-Kakizaki 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 Goto-Kakizaki rats.
authors: Laboratory of Gene Dysregulation and Differentiation, Université Paris Diderot-CNRS EAC 4413, Unit of Functional and Adaptive Biology (BFA), Case 7104, 75205 Paris Cedex 13, France.
authors: Christophe
authors: C
authors: Noll
authors: Gregory
authors: G
authors: Lacraz
authors: Jan
authors: J
authors: Ehses
authors: Josiane
authors: J
authors: Coulaud
authors: Danièle
authors: D
authors: Bailbe
authors: Jean-Louis
authors: JL
authors: Paul
authors: Bernard
authors: B
authors: Portha
authors: Françoise
authors: F
authors: Homo-Delarche
authors: Nathalie
authors: N
authors: Janel
mesh_terms: D000367:Age Factors; D000818:Animals; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D006710:Homocysteine / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006710:Homocysteine; D005978:Glutathione