Diabetogenic effect of N-nitrosomethylurea and N-nitrosomethylurethane in the adult rat.

Abstract

Sodium nitrite and two N-nitroso compounds, N-nitrosomethylurea (NMU) and N-nitrosomethylurethane (NMUT) have been investigated in the adult rat with regard to their in vivo effects on glucose tolerance and insulin response to glucose. Their effects have been compared to the diabetogenic action of streptozotocin (SZ). Glucose challenge (0.5 g/kg) in order to test insulin secretion in vivo gives the same result in the sodium nitrite-treated (25 mg/day during 2 months administered in drinking water) as in the control rats. In the NMU-treated (100 mg/kg i.p.) and in the NMUT-treated (100 mg/kg i.p.) glucose-induced insulin secretion tested 1 or 8 days after drug administration is severely decreased during the second test, especially in the NMUT-treated rats. Rats receiving STZ (35 mg/kg i.v.) exhibit sluggish insulin secretion as soon as the first test. Since in situ formation of nitrites and nitrosamines has been detected in human, one wonders about their role in the aetiology of human diabetes.