LONG-TERM DIABETOGENIC EFFECT OF STREPTOZOTOCIN IN RATS

The long-term effects of streptozotocin (30-70 mg/kg) were studied on plasma glucose and insulin levels, islet morphology, and glucose-stimulated insulin secretion in rats. In addition, the protective effect of short-term (7 days) insulin treatment on streptozotocin-induced diabetes was examined. Streptozotocin administration at dose levels exceeding 40 mg/kg resulted in a long-term, stable hyperglycemia with no insulin response to glucose at 3 months and with a marked derangement of islet morphology (few insulin cells, accumulation of glucagon cells). In contrast, at 30 and 40 mg/kg, streptozotocin induced a transient diabetes. Thus, the blood glucose levels, being elevated at days 1-7, returned to normal levels within 10 days after streptozotocin administration and the glucose-induced insulin secretion, being absent at day 1, was normal at 3 months. Furthermore, the islet morphology was also normal in these groups at 3 months. Short-term (7 days) insulin treatment normalized the long-term diabetes in rats given 50 mg/kg streptozotocin, but not in rats given 60 or 70 mg/kg streptozotocin. Thus, after insulin treatment, all rats receiving 50 mg/kg streptozotocin returned to normoglycemia within the following 2 weeks, and the glucose-induced insulin secretion was normal after 3 months, as was islet morphology. We conclude that (a) spontaneous recovery after streptozotocin is dose dependent and occurs in rats given 30 or 40 mg/kg of the drug, whereas at 50, 60, or 70 mg/kg, streptozotocin induces a stable diabetes; and (b) a short-term (7 days) insulin treatment turns the diabetes induced by streptozotocin at 50 mg/kg into a transient type, whereas the streptozotocin-induced diabetes at 60 or 70 mg/kg is stable despite insulin treatment.