Dysglycemia and Dyslipidemia Models in Nonhuman Primates: Part III. Type I or II Diabetogenic Effects of Streptozocin

Abstract

Streptozocin (STZ), a naturally occurring glucosamine-nitrosourea compound, has been used for diabetogenic induction in animals for diabetic research due to its high toxicity to pancreatic beta cells. This study was to evaluate the diabetogenic effects of STZ by multiple low doses or by single high dose in normoglycemic Non-Human Primates (NHPs). Each monkey in the 1st group (n=6) was intravenously administered with 7.5 to 15 mg/kg STZ once every 2 to 4 weeks until successful induction of hyperglycemia or until the end of this 28-week study. In the 2nd group (n=7) each monkey was intravenously injected with 35 mg/kg STZ once only. Plasm glucose, insulin and lipid levels were monitored weekly during the study. The hyperglycemic responses to STZ were more severe in the NHPs treated with the single high dose. Among them one animal died on the 2nd day after STZ dosing. Compared with STZ multiple low doses, single high dose caused much severe insulin depletion, similar to Type I diabetes. In addition, beta-cell sensitivity to STZ toxicity varied obviously among individual monkeys, some highly sensitive and some almost no response at all. STZ also resulted in abnormal response to the intravenous glucose tolerance test (ivGTT). These results demonstrate that hyperglycemic levels among STZ-treated animals varied and differed significantly after either single high dose or multiple low doses. Our data may help researchers to understand the diabetogenic process and variability of STZ induction in NHPs and to choose a severe or moderate model for their research.