Studies on Sex Dependency of B-cell Susceptibility to Streptozotocin in a Rat Model of Type II Diabetes Mellitus

Abstract

Non-insulin-dependent (Type 2) diabetes in the rat can be induced by a neonatal injection of streptozotocin (STZ). At adult age male rats are more severely affected than female rats. Such difference could be due to a sex-related dissimilarity in susceptibility to STZ; this possibility was investigated in the present study. Incubation of isolated islets from male and female rats with STZ for 30 min, followed by tissue culture for 24 h, induced a dose-dependent decrease in insulin content that was similar in islets of both sexes. STZ in vivo, injected i.p on the second day of life, markedly enhanced blood glucose levels and reduced pancreatic insulin content when measured 2-12 days after the STZ injection. The parameters of B-cell damage did not differ, however, between male and female pups. Testosterone treatment, when started two days after the STZ injection, significantly accentuated hyperglycemia in both sexes during the second week of life. Body weight and pancreatic insulin content were not affected by the testosterone treatment. In conclusion, B-cell susceptibility to STZ in vitro or in vivo, during the neonatal period, is not influenced by gender. The hyperglycemic effect of testosterone indicates that the rise in androgens, starting with puberty, is at least partially responsible for a more severe diabetic state in male than in female rats at adult age.