Hepatic and renal metabolism of methyl groups and homocysteine are altered by diabetes and glucocorticoid treatment in rats

Abstract

Homocysteine (Hcys) is produced from methionine via transmethylation reactions. The supply and utilization of methyl groups for transmethylation reactions are proposed to be regulated by an abundant hepatic protein, glycine N-methyltransferase (GNMT). Our previous short-term (5–7 d) studies show that GNMT activity and abundance are increased in streptozotocin-induced diabetic rats. However, a concurrent increase in remethylation by betaine-homocysteine methyltransferase may contribute to a decrease in plasma Hcys levels. Elevated plasma Hcys is an independent risk factor for the development of cardiovascular disease (CVD). Elevated plasma Hcys levels are frequently observed in diabetic patients, particularly those with diminished renal function, and the diabetic condition itself is a risk factor for CVD. Thus, the aim of the current study was to investigate temporal changes in hepatic and renal methyl group and Hcys metabolism past the acute diabetic stage. Rat treatments included injection of streptozotocin (60 mg/kg BW) or dexamethasone (DEX, 1 mg/kg BW) to induce a diabetic/gluconeogenic state. Renal GNMT activity and abundance were elevated by DEX. By two weeks, plasma Hcys levels were significantly decreased and hepatic GNMT activity and abundance were markedly increased in the diabetic rat. These results indicate that renal, like hepatic, methyl group metabolism was significantly altered. Future research studies should focus on a more thorough evaluation of hepatic and renal methyl group and Hcys metabolism to understand the temporal progression from hypohomocysteinemia to hyperhomocysteinemia during diabetes. (Support: Am. Diab. Assoc.)