Abstract
An elevation in the concentration of total plasma homocysteine is known to be an independent risk factor for the development of vascular disease. Alterations in homocysteine metabolism have also been observed clinically in diabetic patients. Patients with either type 1 or type 2 diabetes who have signs of renal dysfunction tend to exhibit elevated total plasma homocysteine levels, whereas type 1 diabetic patients who have no clinical signs of renal dysfunction have lower than normal plasma homocysteine levels. The purpose of this study was to investigate homocysteine metabolism in a type 1 diabetic animal model and to examine whether insulin plays a role in its regulation. Diabetes was induced by intravenous administration of 100 mg/kg streptozotocin to Sprague-Dawley rats. We observed a 30% reduction in plasma homocysteine in the untreated diabetic rat. This decrease in homocysteine was prevented when diabetic rats received insulin. Transsulfuration and remethylation enzymes were measured in both the liver and the kidney. We observed an increase in the activities of the hepatic transsulfuration enzymes (cystathionine beta-synthase and cystathionine gamma-lyase) in the untreated diabetic rat. Insulin treatment normalized the activities of these enzymes. The renal activities of these enzymes were unchanged. These results suggest that insulin is involved in the regulation of plasma homocysteine concentrations by affecting the hepatic transsulfuration pathway, which is involved in the catabolism of homocysteine.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / drug effects
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5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / metabolism
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Animals
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Betaine-Homocysteine S-Methyltransferase
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Blood Glucose / drug effects
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Blood Glucose / metabolism
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Body Weight / drug effects
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Creatinine / blood
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Cystathionine beta-Synthase / drug effects
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Cystathionine beta-Synthase / metabolism
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Cystathionine gamma-Lyase / drug effects
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Cystathionine gamma-Lyase / metabolism
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Diabetes Mellitus, Experimental / drug therapy
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Diabetes Mellitus, Experimental / metabolism
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Diabetes Mellitus, Experimental / physiopathology*
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Diabetes Mellitus, Type 1 / drug therapy
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Diabetes Mellitus, Type 1 / metabolism
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Diabetes Mellitus, Type 1 / physiopathology
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Disease Models, Animal
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Eating / drug effects
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Homocysteine / blood
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Homocysteine / drug effects*
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Homocysteine / metabolism*
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Hypoglycemic Agents / therapeutic use*
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Insulin / therapeutic use*
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Kidney / drug effects
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Kidney / enzymology
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Liver / drug effects
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Liver / enzymology
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Male
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Methylenetetrahydrofolate Reductase (NADPH2)
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Methyltransferases / drug effects
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Methyltransferases / metabolism
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Oxidoreductases Acting on CH-NH Group Donors / drug effects
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Oxidoreductases Acting on CH-NH Group Donors / metabolism
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Rats
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Rats, Sprague-Dawley
Substances
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Blood Glucose
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Hypoglycemic Agents
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Insulin
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Homocysteine
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Creatinine
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Oxidoreductases Acting on CH-NH Group Donors
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Methylenetetrahydrofolate Reductase (NADPH2)
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Methyltransferases
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5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
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Betaine-Homocysteine S-Methyltransferase
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Bhmt protein, rat
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Cystathionine beta-Synthase
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Cystathionine gamma-Lyase