The Diabetogenic Effects of Streptozotocin in Mice are Prolonged and Inversely Related to Age

Autor: William J. Riley, McConnell Tj, Judith V. McLaughlin, Glen Taylor, Noel K. Maclaren
Rok vydání: 1981
Předmět:
Zdroj: Diabetes. 30:718-723
ISSN: 1939-327X
0012-1797
DOI: 10.2337/diab.30.9.718
Popis: 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 insulincontaining 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 nor for SZ as the agent inducing β-cell injury. The induction of β-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 β-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 outgrowing 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 mice when SZ was given, may have implications for understanding the apparent heterogeneity of human diabetes mellitus.
Databáze: OpenAIRE