Homocysteine metabolism in ZDF (type 2) diabetic rats

被引:74
|
作者
Wijekoon, EP
Hall, B
Ratnam, S
Brosnan, ME
Zeisel, SH
Brosnan, JT [1 ]
机构
[1] Mem Univ Newfoundland, Dept Biochem, St John, NF A1B 3X9, Canada
[2] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
关键词
D O I
10.2337/diabetes.54.11.3245
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Mild hyperhomocysteinemia is a risk factor for many diseases, including cardiovascular disease. We determined the effects of insulin resistance and of type 2 diabetes on homocysteine (Hcy) metabolism using Zucker diabetic fatty rats (ZDF/Gmi fa/fa and ZDF/Gmi fa/?). Plasma total Hcy was reduced in ZDF fa/fa rats by 24% in the prediabetic insulin-resistant stage, while in the frank diabetic stage there was a 59% reduction. Hepatic activities of several enzymes that play a role in the removal of Hcy: cystathionine beta-synthase (CBS), cystathionine gamma-lyase, and betaine:Hcy methyltransferase (BHMT) were increased as was methionine adenosyltransferase. CBS and BHMT mRNA levels and the hepatic level of S-adenosylmethionine were also increased in the ZDF fa/fa rats. Studies with primary hepatocytes showed that Hcy export and the trans-sulfuration flux in cells from ZDF fa/fa rats were particularly sensitive to betaine. Interestingly, liver betaine concentration was found to be significantly lower in the ZDf fa/fa rats at both 5 and 11 weeks. These results emphasize the importance of betaine metabolism in determining plasma Hcy levels in type 2 diabetes.
引用
收藏
页码:3245 / 3251
页数:7
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