The diabetogenic effects of streptozotocin in mice are prolonged and inversely related to age.
Single "subdiabetogenic" doses of streptozotocin (SZ), when given to young male CD-1 mice, produced a delayed onset of hyperglycemia dependent on the dose of SZ and on the age of the mice. The effect was markedly reduced or absent in older mice given the same dose of SZ per kg of body weight. Histologic examination of the pancreas of these animals revealed that SZ induced greater damage to the islets of the young mice compared with older mice. In addition to the characteristic findings of a decrease in insulin-containing cells and an increase in glucagon- and pancreatic polypeptide-containing cells there was evidence of new islet formation. Delayed-onset hyperglycemia was also induced in young inbred DBA/2J, C57BL/KsJ, and SWR/J mice with single SZ doses as well as with alloxan in young CD-1 mice, indicating that the effect was not specific for CD-1 mice not for SZ as the agent inducing beta-cell injury. The induction of beta-cell autoimmunity did not appear to be important in the delayed diabetogenic effect of SZ, since insulitis was rare and followed the onset of hyperglycemia when seen, and islet cell autoantibodies were not found. Rather, SZ induced more beta-cell destruction in young animals than in older mice, and the continued somatic growth of the former suggests that the delayed hyperglycemia was due to an out-growing of a reduced insulin supply. That mild to severe diabetes could be induced by the same dose of SZ/kg, depending only on the age of the mice when SZ was given, may have implications for understanding the apparent heterogeneity of human diabetes mellitus.
D000375:Aging; D000496:Alloxan; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005455:Fluorescent Antibody Technique; D005951:Glucose Tolerance Test; D007328:Insulin / Q000032:analysis; D007330:Insulin Antibodies / Q000032:analysis; D007515:Islets of Langerhans / Q000032:analysis; D008099:Liver / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013045:Species Specificity; D013311:Streptozocin
D007328:Insulin; D007330:Insulin Antibodies; D013311:Streptozocin; D000496:Alloxan