Homocysteine metabolism in ZDF (type 2) diabetic rats.
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 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 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.
Wijekoon
Enoka P
EP
Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
Hall
Beatrice
B
Ratnam
Shobhitha
S
Brosnan
Margaret E
ME
Zeisel
Steven H
SH
Brosnan
John T
JT
D000818:Animals; D001622:Betaine / Q000378:metabolism; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D022781:Hepatocytes / Q000378:metabolism; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology; D008715:Methionine / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D012333:RNA, Messenger; D051381:Rats; D011924:Rats, Zucker
D010713:Phosphatidylcholines; D012333:RNA, Messenger; D006710:Homocysteine; D001622:Betaine; D008715:Methionine