Diabetogenic Effect of Streptozotocin in the Rat During the Perinatal Period

Abstract

The diabetogenic effect of streptozotocin was investigated in the rat during the fetal and neonatal life. Streptozotocin was directly injected in the vitellin vein of the fetus or in the saphenous vein of the neonate. In the 21.5 day old fetus, diabetogenic activity was demonstrated with a single dose of 100 μg/gm. administered the day before, and this was indicated by a fall in the pancreatic insulin content to 20 per cent and a lowering of the plasma insulin to 60 per cent of the controls. A single dose (100 μg/gm.) of streptozotocin administered on the day of birth produced an overt diabetes in the neonate: the maximal fall in the pancreatic insulin content (7 per cent of the controls) was observed four days after the streptozotocin injection, during the highest blood glucose level (300 per cent of the controls). A significant increase in the pancreatic glucagon content was observed twenty-four hours after the maximal insulin depletion. Liver glycogen content was occasionally decreased. More severe diabetes was obtained by two streptozotocin injections (50μg/gm.), with lowest pancreatic and highest blood glucose levels at 1 per cent and 60 per cent, respectively. A clearcut drop of the plasma insulin/glucose ratio was observed in the drug-treated animals. Three weeks after injection(s), basal blood glucose and plasma insulin levels were normal, although impairment of insulin secretion still appeared after glucose load and insulin pancreatic content was still slightly lower. A rapid and spontaneous, if not quite complete recovery, is a characteristic pattern of the streptozotocin diabetes in the neonate as compared to that in the adult.