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Characterization of methyl group metabolism in the non‐obese diabetic (NOD) mouse
Author(s) -
Neuman Joshua Charles,
Nieman Kristin M,
Schalinske Kevin L
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.915.11
Subject(s) - nod , medicine , endocrinology , homocysteine , methyltransferase , nod mice , metabolism , diabetes mellitus , methylation , dna methylation , biology , chemistry , biochemistry , dna , gene expression , gene
Perturbed methyl group metabolism leads to elevated circulating levels of homocysteine, an independent risk factor for cardiovascular disease, as well as DNA hypomethylation. A streptozotocin‐induced type 1 diabetic rat model showed disrupted methyl group metabolism, characterized by increased levels of glycine N‐ methyltransferase (GNMT), DNA hypomethylation, and hypohomocysteinemia. The present study examined similar measures of methyl group metabolism in the genetic non‐obese diabetic (NOD) mouse model. At 24 wk of age, NOD and ICR (control) mice were sacrificed and blood, liver, and kidney tissue were collected. NOD mice displayed 59% (P < 0.05) greater GNMT activity compared to the ICR mice. A correlation between both hepatic GNMT activity (r = 0.81, P < 0.002) and DNA hypomethylation (r = 0.59, P ≤ 0.05) with plasma glucose concentrations was also observed. Plasma homocysteine levels in the blood decreased by 53% in the NOD group (P < 0.005) compared to the controls. However, phosphatidylethanolamine N ‐methyltransferase (PEMT) was down‐regulated in NOD mice, compared to its increase with streptozotocin treatment. This indicates that a genetic and chemically induced model for type 1 diabetes exhibit similar, but not entirely consistent, findings with respect to disrupted methyl group metabolism. Grant Funding Source : NIH HD057315