Characterizing the induction of diabetes in juvenile cynomolgus monkeys with different doses of streptozotocin

Abstract

Juvenile (2-23 years old) cynomolgus monkeys are frequently used as recipients in non-human primate islet transplantation studies. The aim of this study was to examine the effects of different doses of streptozotocin (STZ), and find the optimal dose for inducing diabetes in these monkeys. Fifteen juvenile (2-3 years old) cynomolgus monkeys were separated into three groups and administered with different doses of STZ (100, 68 or 60 mg kg(-1)). Basal and glucose-stimulated blood glucose, insulin, and C-peptide levels, as well as body weights were monitored. Hepatic and renal function tests and pancreatic immunohistochemistry were performed before and after STZ treatment. Monkeys treated with both 100 and 68 mg kg(-1) of STZ exhibited continuous hyperglycemia, which coincided with a nearly complete loss of islet β-cells. Two monkeys received 60 mg kg(-1) of STZ, but only one became completely diabetic. During the first week following STZ treatment, hepatic and renal function slightly increased in these three groups. However, 24 hours post-STZ, serum total bile acid levels were significantly increased in monkeys treated with 100 mg kg(-1) than those treated with 68 mg kg(-1) of STZ (P<0.05). These data suggest that 100 mg kg(-1) and 68 mg kg(-1) of STZ can safely induce diabetes in cynomolgus monkeys aged 2-3 years, but 68 mg kg(-1) of STZ, rather than 100 mg kg(-1) of STZ, may be more appropriate for inducing diabetes in these monkeys. Furthermore, body surface area, rather than body weight, was a more reliable determinant of dosage, where 700 mg m(-2) of STZ should be the lower limit for inducing diabetes in juvenile monkeys.