Insulin secretion in neonatally streptozotocin-injected mice

Streptozotocin (150 mg/kg) was given intraperitoneally at the age of two and three days to neonatal mice. At three weeks of age, these streptozotocin-treated mice were hyperinsulinemic but normoglycemic when compared to controls indicating a relative inhibition of insulin action. From the age of five weeks, the streptozotocin-treated mice were hyperglycemic. The diabetes prevalence in streptozotocin-treated mice started to increase between three and five weeks of age, to finally become approximately 25%. At five weeks of age, the plasma insulin response to glucose was still normal in streptozotocin-treated mice, whereas carbachol-induced insulin secretion was impaired with no difference between those with and those without diabetes. At 10 weeks of age, all diabetics had impaired glucose- and carbachol-induced increase in plasma insulin levels, whereas streptozotocin-treated mice without diabetes had plasma insulin responses within the normal range. This study shows that intraperitoneal injection of streptozotocin to neonatal mice results in a permanent diabetes prevalence of approximately 25%. The study also suggests that during the progression to diabetes in streptozotocin-injected neonatal mice, impairment of glucose-stimulated insulin secretion occurs but this impairment is initially compensated. In contrast, a defect in carbachol-stimulated insulin secretion is not compensated and therefore visible earlier.