Streptozotocin Resistance of the Genetically Diabetic KK Mouse

Abstract

Intraperitoneally administered streptozotocin (100 mg. per kilogram) produced hyperglycemia (higher than 200 mg. per 100 ml.) in 100 per cent of C57BL, but in none of KK mice. Pretreat-ment with phentolamine (50 mg. per kilogram), an α-adrenergic blocking agent, decreased resistance of KK mice to the diabetogenic action of streptozotocin. On the other hand, pre-treatment with propranolol (10 mg. per kilogram), a β-adrenergic blocking agent, induced resistance to streptozotocin in C57BL mice. This effect of propranolol was potentiated by administration of epinephrine (1 mg. per kilogram). These findings suggest that the α-adrenergic system protects pancreatic β cells from cytotoxic action by streptozotocin, indicating a predominance of the α-adrenergic system in diabetic mice of the KK strain.