Prolonged refractoriness to the diabetogenic action of streptozotocin in mice

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 $\text{C57BL}\text{6}$ and $\text{C57BL}\text{10}$ (sensitive) strains. The $\text{C3H}\text{HeJ}$ and $\text{C3H}\text{eb}$ (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. $\text{C3H}\text{HeJ}$ (resistant) mice showed a smaller fall in immunoreactive insulin pancreatic content and less severe damage of pancreatic islets on histologic examination, when compared to $\text{C57BL}\text{6}$ (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.