Diabetogenic effects of N-nitrosomethylurea in rats

The influence of a single i.v. injection of 75 or 175 mg N-nitrosomethylurea (NMU)/kg into Wistar rats on plasma glucose, i.p. glucose tolerance, plasma insulin and glucagon, glucose stimulated insulin secretion and release as well as on the biosynthesis of insulin in isolated pancreatic islets have been investigated at set intervals between the 3rd day and the 6th week post injectionem. At the end of the experimental period all NMU-treated animals were alive but had significantly reduced body mass. All animals remained normoglycemic even after the glucose load. 3 days after drug application plasma insulin decreased only insignificantly in the 175 mg NMU-group, whereas plasma glucagon was significantly reduced in both drug-groups; after 3 and 6 weeks the reduction of plasma glucagon was still about 30 percent. In isolated islets the glucose stimulated insulin secretion, the percent stimulation of insulin release and insulin biosynthesis were significantly decreased.