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Am J Physiol Endocrinol Metab 291: E1235-E1242, 2006. First published July 11, 2006; doi:10.1152/ajpendo.00237.2006
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Folate status modulates the induction of hepatic glycine N-methyltransferase and homocysteine metabolism in diabetic rats

Kristin M. Nieman,1 Cara S. Hartz,1 Sandra S. Szegedi,2 Timothy A. Garrow,2 Janet D. Sparks,3 and Kevin L. Schalinske1

1Department of Food Science and Human Nutrition, Iowa State University, Ames, IA; 2Department of Food Science and Human Nutrition and the Division of Nutritional Sciences, University of Illinois, Urbana, Illinois; and 3Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York

Submitted 18 May 2006 ; accepted in final form 2 July 2006

A diabetic state induces the activity and abundance of glycine N-methyltransferase (GNMT), a key protein in the regulation of folate, methyl group, and homocysteine metabolism. Because the folate-dependent one-carbon pool is a source of methyl groups and 5-methyltetrahydrofolate allosterically inhibits GNMT, the aim of this study was to determine whether folate status has an impact on the interaction between diabetes and methyl group metabolism. Rats were fed a diet containing deficient (0 ppm), adequate (2 ppm), or supplemental (8 ppm) folate for 30 days, after which diabetes was initiated in one-half of the rats by streptozotocin treatment. The activities of GNMT, phosphatidylethanolamine N-methyltransferase (PEMT), and betaine-homocysteine S-methyltransferase (BHMT) were increased about twofold in diabetic rat liver; folate deficiency resulted in the greatest elevation in GNMT activity. The abundance of GNMT protein and mRNA, as well as BHMT mRNA, was also elevated in diabetic rats. The marked hyperhomocysteinemia in folate-deficient rats was attenuated by streptozotocin, likely due in part to increased BHMT expression. These results indicate that a diabetic state profoundly modulates methyl group, choline, and homocysteine metabolism, and folate status may play a role in the extent of these alterations. Moreover, the upregulation of BHMT and PEMT may indicate an increased choline requirement in the diabetic rat.

choline; phosphatidylethanolamine; betaine-homocysteine S-methyltransferase



Address for reprint requests and other correspondence: K. L. Schalinske, Dept. of Food Science and Human Nutrition, Iowa State University, 220 MacKay Hall, Ames, IA 50011 (e-mail: kschalin{at}iastate.edu)




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