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 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 beta 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.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D013311:Streptozocin / Q000633:toxicity; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin