Prolonged refractoriness to the diabetogenic action of streptozotocin in mice

Abstract

A single intraperitoneal injection of 5 mg (250 mg/kg body wt) streptozotocin induced overt diabetes within 48 hr in male, 6-week-old mice of C57BL 6 and C57BL 10 (sensitive) strains. The C3H HeJ and C3H eb (resistant) strains exhibited a progressive delayed-onset hyperglycemia which required 6 weeks to reach the level seen within only 48 hr in sensitive strains. Resistance to SZ-induced diabetes was not related to changes in body weights or different pharmacokinetics of the drug. C3H HeJ (resistant) mice showed a smaller fall in immunoreactive insulin pancreatic content and less severe damage of pancreatic islets on histologic examination, when compared to C57BL 6 (sensitive) mice during the first week post-SZ. These results suggest that strain-related resistance to SZ-induced diabetes may be mediated at the level of the β cell's responsiveness to the cytotoxic action of the drug. This very simple experimental tool may be of value in monitoring the period before the onset of overt insulin-deficient diabetes and for probing the nature of factors that constitute a genetically resistant pancreas, understanding of which could aid management of diabetes mellitus in humans.