Altered methionine metabolism in streptozotocin-diabetic rats.
We examined the origin of hypermethioninaemia in streptozotocin-diabetic rats. In rats administered streptozotocin over a range from 55 to 75 mg/kg, the dose of drug injected correlated directly with the plasma methionine concentration and inversely with the plasma insulin level. Although insulin administration prevented hypermethioninaemia in streptozotocin-diabetic rats, discontinuing insulin treatment resulted in a time-dependent increase in the plasma methionine level. Plasma methionine concentration was, however, normal in insulin-deprived BB Wistar rats despite severe hyperglycaemia. Thus, although insulin deficiency may be a contributing factor, it does not cause hypermethioninaemia independent of other drug-related effects. Administering a loading dose of methionine (100 mg/kg) indicated that streptozotocin-diabetic rats have a reduced metabolic capacity. Since dietary intake is the primary source of methionine, it is likely that hyperphagia combined with limited disposal produces hypermethioninaemia. Methionine is the most toxic amino-acid; therefore, metabolic studies using the streptozotocin model of insulin deficiency must be interpreted with caution.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D003553:Cystine / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000201:enzymology; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D008715:Methionine / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D003553:Cystine; D008715:Methionine; D003542:Cystathionine gamma-Lyase