title: Insulin administration abrogates perturbation of methyl group and homocysteine metabolism in streptozotocin-treated type 1 diabetic rats.
abstract: Modifications in methyl group and homocysteine metabolism are associated with a number of pathologies, including vascular disease, cancer, and neural tube defects. A diabetic state is known to alter both methyl group and homocysteine metabolism, and glycine N-methyltransferase (GNMT) is a major regulatory protein that controls the supply and utilization of methyl groups. We have shown previously that diabetes induces GNMT expression and reduces plasma homocysteine pools by stimulating both its catabolism and folate-independent remethylation. This study was conducted to determine whether insulin plays a role in the control of homocysteine concentrations and GNMT as well as other key regulatory proteins. Male Sprague-Dawley rats were randomly assigned to one of three groups: control, streptozotocin (STZ)-induced diabetic (60 mg/kg body wt), and insulin-treated diabetic (1.0 U bid). After 5 days, rats were anesthetized (ketamine-xylazine) for procurement of blood and tissues. A 1.5-fold elevation in hepatic GNMT activity and hypohomocysteinemia in diabetic rats was completely prevented by insulin treatment. Additionally, diabetes-mediated alterations in methionine synthase, phosphatidylethanolamine N-methyltransferase, and DNA methylation were also prevented by insulin. We hypothesize that the concentration of blood glucose may represent a regulatory signal to modify GNMT and homocysteine. In support of this, blood glucose concentrations were negatively correlated with total plasma homocysteine (r = -0.75, P < 0.001) and positively correlated with GNMT activity (r = 0.77, P < 0.001). Future research will focus on further elucidating the role of glucose or insulin as a signal for regulating homocysteine and methyl group metabolism.
authors: Dept. of Food Science and Human Nutrition, Iowa State University, Ames, USA.
authors: Kristin M
authors: KM
authors: Nieman
authors: Kevin L
authors: KL
authors: Schalinske
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D019175:DNA Methylation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D050938:Glycine N-Methyltransferase / Q000378:metabolism*; D006710:Homocysteine / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D007328:Insulin; D006710:Homocysteine; D050938:Glycine N-Methyltransferase