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.