Induction of diabetes in cynomolgus monkeys with high-dose streptozotocin - Adverse effects and early responses
Induction of diabetes in cynomolgus monkeys with high-dose streptozotocin - Adverse effects and early responses
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DOI：
10.1097/01.mpa.0000235307.04110.a2
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发表时间：
2006-10-01
期刊：
影响因子：
2.9
通讯作者：
Cooper, David K. C.
中科院分区：
文献类型：
--
作者：
Rood, Pleunie P. M.;Bottino, Rita;Cooper, David K. C.
目的：链脲佐菌素（STZ）已被广泛用于在非人灵长类动物中诱导糖尿病，但已发现很难在没有严重不良反应的情况下实现完全糖尿病。我们研究了不同类型和剂量的STZ，以找到一种安全地诱导食蟹猴完全性糖尿病的方法。5只猴子接受常规STZ（Sigma），剂量为1250 mg/m2（“高剂量”; n = 4）或60 mg/kg（“低剂量”; n = 1;第1组）。5只猴子接受150 mg/kg的Zanosar STZ（Sicor Pharmaceuticals，Irvine，CA）（高剂量; n = 5;组2）。结果：高关闭组I猴子变成完全糖尿病（n = 4），但在4只猴子中的3只中观察到蛋白丢失性肾病。接受60 mg/kg STZ的猴子没有完全患糖尿病（C肽，> 1.86 ng/mL）。第2组（高剂量赞普治疗）的猴子完全患糖尿病，但没有明显的不良反应。在所有高剂量STZ治疗的猴子中记录了对STZ的三相血糖反应。结论：（1）高剂量扎诺沙链脲佐菌素可安全地诱导食蟹猴糖尿病，且无不良反应。(2)三相血糖反应提示糖尿病的完全诱导。
Objectives: Streptozotocin (STZ) has been widely used to induce diabetes in nonhuman primates, although it has been found difficult to achieve complete diabetes without serious adverse effects. We have investigated different types and dosages of STZ to find a way to safely induce complete diabetes in cynomolgus monkeys.Methods: After adequate hydration, 10 monkeys received STZ. Five monkeys received conventional STZ (Sigma) at a dosage of 1250 mg/m(2) ("high dose"; n = 4) or 60 mg/kg ("low dose"; n = 1; Group 1). Five monkeys received Zanosar STZ (Sicor Pharmaceuticals, Irvine, CA) at 150 mg/kg (high dose; n = 5; Group 2).Results: High-close Group I monkeys became completely diabetic (n = 4), but a protein-losing nephropathy was observed in 3 of the 4 monkeys. The monkey that received 60 mg/kg STZ failed to become fully diabetic (C-peptide, > 1.86 ng/mL). Group 2 (high-dose Zanosar-treated) monkeys became completely diabetic but with no apparent adverse effects. A triphasic blood glucose response to STZ was documented in all the high-dose STZ-treated monkeys. Low-dose STZ failed to result in a triphasic response.Conclusions: (1) High-dose Zanosar STZ induced diabetes safely in cynomolgus monkeys without adverse effects. (2) A triphasic blood Glucose response suggested the complete induction of diabetes.