Diabetogenic effects of n-nitrosomethylurea in the chinese hamster

To evaluate the role of the glucose residue of the diabetogenic substance streptozotocin, the effect of its aglucone derivate N-nitrosomethylurea was tested in Chinese hamsters. At a dose of 50 mg/kg body weight of N-nitrosomethylurea a triphasic blood glucose curve was recorded with an initial hyperglycaemic peak after 3 hours followed by a decrease at 6 hours. After 24 hours and during the following days the values were moderately elevated. There was a high mortality in the diabetic animals, about 80 per cent of them dying within one week. The approximate L.D. 50 of N-nitrosomethylurea injected intraperitoneally in non-fasting adult animals was about 125 mg/kg body weight at an observation time of 48 hours. On light microscopy, degenerative changes with nuclear pyknosis were seen after 3 hours in the pancreatic islet cells, followed by cellular disintegration. Both beta-, alpha2- and alpha1-cells were obviously affected. Pretreatment with 500 mg nicotinamide/kg body weight given intraperitoneally 10 minutes before the injection of N-nitrosomethylurea inhibited and hyperglycaemia and seemed to prevent the injurious effects of N-nitrosomethylurea on the islet cells. The results show that the glucose residue of the streptozotocin molecule is not necessary for the induction of diabetes in Chinese hamsters, but it seems to increase the selectivity of the toxic effects for the islet cells. This is a clear advantage in studies of experimental diabetes, especially when longer observation periods are desired.