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 Posted: Wed Oct 29, 2008 8:37 pm Post subject: Type I diabetes leads to tissue-specific DNA hypomethylation |
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J Nutr. 2008 Nov;138(11):2064-9. Links
Type I diabetes leads to tissue-specific DNA hypomethylation in male
rats.Williams KT, Garrow TA, Schalinske KL.
Department of Food Science and Human Nutrition, and the
Interdepartmental Graduate Program in Nutritional Sciences, Iowa State
University, Ames, IA 50011, USA.
Numerous perturbations of methyl group and homocysteine metabolism
have been documented as an outcome of diabetes. It has also been
observed that there is a transition from hypo- to hyperhomocysteinemia
in diabetes, often concurrent with the development of nephropathy. The
objective of this study was to characterize the temporal changes in
methyl group and homocysteine metabolism in the liver and kidney and
to determine the impact these alterations have on DNA methylation in
type 1 diabetic rats. Male Sprague-Dawley rats were injected with
streptozotocin (60 mg/kg body weight) to induce diabetes and samples
were collected at 2, 4, and 8 wk. At 8 wk, hepatic and renal betaine-
homocysteine S-methyltransferase activities were greater in diabetic
rats, whereas methionine synthase activity was lower in diabetic rat
liver and kidney did not differ. Cystathionine beta-synthase abundance
was greater in the liver but less in the kidney of diabetic rats. Both
hepatic and renal glycine N-methyltransferase (GNMT) activity and
abundance were greater in diabetic rats; however, changes in renal
activity and/or abundance were present only at 2 and 4 wk, whereas
hepatic GNMT was induced at all time points. Most importantly, we have
shown that genomic DNA was hypomethylated in the liver, but not the
kidney, in diabetic rats. These results suggest that diabetes-induced
perturbations of methyl group and homocysteine metabolism lead to
functional methyl deficiency, resulting in the hypomethylation of DNA
in a tissue-specific fashion.
PMID: 18936199 [PubMed - in process] |
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