Juvenile(2-3 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--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.
ZOU ChunLinWANG JiaYinWANG ShuYanHUANG FenREN ZhenHuaCHEN ZhiGuoZHANG YU
