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...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-l). Basal and glucose-stimulated blood glucose, in- sulin, and C-peptide levels, as well as body weights were monitored. Hepatic and renal function tests and pancreatic immuno- histochemistry were performed before and after STZ treatment. Monkeys treated with both 100 and 68 mg kg-1 of STZ exhib- ited continuous hyperglycemia, which coincided with a nearly complete loss of islet 13-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 func- tion slightly increased in these three groups. However. 24 hours post-STZ, serum total bile acid levels were significantly in- creased in monkeys treated with 100 mg kg-1 than those treated with 68 mg kg-I 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.展开更多
基金supported by the National Basic Research Program of China(Grant No.2007CB947704)the National High Technology Research and Development Program of China(Grant Nos. 2006AA02A112 and 2006AA02A116)High Level Talent Fund of the Beijing Healthcare System(Grant No.2009-2-14)
文摘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-l). Basal and glucose-stimulated blood glucose, in- sulin, and C-peptide levels, as well as body weights were monitored. Hepatic and renal function tests and pancreatic immuno- histochemistry were performed before and after STZ treatment. Monkeys treated with both 100 and 68 mg kg-1 of STZ exhib- ited continuous hyperglycemia, which coincided with a nearly complete loss of islet 13-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 func- tion slightly increased in these three groups. However. 24 hours post-STZ, serum total bile acid levels were significantly in- creased in monkeys treated with 100 mg kg-1 than those treated with 68 mg kg-I 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.