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Homocysteine Metabolism in ZDF (Type 2) Diabetic Rats

机译:ZDF(2型)糖尿病大鼠的同型半胱氨酸代谢

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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 pre-diabetic 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 β-synthase (CBS), cystathionine γ-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 transsulfuration 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.
机译:轻度高半胱氨酸血症是许多疾病(包括心血管疾病)的危险因素。我们使用Zucker糖尿病脂肪大鼠(ZDF / Gmi fa / fa和ZDF / Gmi fa /α)确定了胰岛素抵抗和2型糖尿病对同型半胱氨酸(Hcy)代谢的影响。在糖尿病前期胰岛素抵抗阶段,ZDF fa / fa大鼠血浆总Hcy降低了24%,而在坦率糖尿病阶段则降低了59%。与蛋氨酸腺苷基转移酶一样,在去除Hcy中起作用的几种酶的肝活性也增加了:胱硫醚β-合酶(CBS),胱硫醚γ-裂合酶和甜菜碱:羟丙基甲基转移酶(BHMT)。 ZDF fa / fa大鼠的CBS和BHMT mRNA水平以及S-腺苷甲硫氨酸的肝水平也升高。对原代肝细胞的研究表明,ZDF fa / fa大鼠细胞中的Hcy出口和转硫通量对甜菜碱特别敏感。有趣的是,在第5周和第11周时,ZDf fa / fa大鼠的肝脏甜菜碱浓度均显着降低。这些结果强调了甜菜碱代谢在确定2型糖尿病血浆Hcy水平中的重要性。

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