Long-term changes in the diabetic state induced by different doses of streptozotocin in rats.

The long-term effects of different doses (0, 25, 35, 45, 55, 65 and 100 mg/kg) of streptozotocin (STZ) in male Wistar rats had been followed over a 16 week period. The weight-gain curve and the epididymal fat pad weight were significantly different (P less than 0.05) from control after 1 week with the 65 and 100 mg/kg doses and after 4 weeks with the 45 and 55 mg/kg doses; there were no significant changes with the 25 and 35 mg/kg doses even after 16 weeks. An i.v. glucose tolerance test (0.5 g/kg) was performed at 1, 4 or 16 weeks after the injection of STZ. The basal levels of glucose were significantly elevated (P less than 0.05) after 1 week with the greater than or equal to 55 mg/kg doses, and after 16 weeks with the greater than or equal to 45 mg/kg doses; there was also an overall increase in the basal glucose levels between 1 and 16 weeks in rats treated with the greater than or equal to 45 mg/kg doses. The basal insulin levels were significantly decreased (P less than 0.05) after 1 week with the greater than or equal to 65 mg/kg doses, after 4 weeks with the greater than or equal to 55 mg/kg doses and after 16 weeks with the greater than or equal to 35 mg/kg doses. The insulin peak 2 min after the glucose load was significantly less (P less than 0.05) after 1 week with the greater than or equal to 35 mg/kg doses and after 16 weeks with the greater than or equal to 25 mg/kg doses. The use of an insulinogenic index to assess the insulin secretory capacity showed a significant decrease (P less than 0.05) for the greater than or equal to 35 mg/kg doses at each tested time; with the 45 mg/kg dose, there was a further significant decrease (P less than 0.01) between the first and sixteenth week. The present long-term studies showed that there is a progressive deterioration in the glucose tolerance and insulin secretion after the injection of different doses of STZ. Furthermore, changes in glucose-insulin interrelationships over time suggest that the insulin insensitivity previously described in STZ diabetic rats might be only an early transient phenomenon.