Theriault B R, Thistlethwaite J R, Levisetti M G, Wardrip C L, Szot G, Bruce D S, Rilo H, Li X, Gray G S, Bluestone J A, Padrid P A
Department of Medicine, University of Chicago, Illinois 60637, USA.
Transplantation. 1999 Aug 15;68(3):331-7. doi: 10.1097/00007890-199908150-00003.
Insulin-dependent diabetes mellitus (IDDM) is the second most prevalent chronic illness of children. Investigation of the treatment of IDDM is hindered by the lack of a reproducible and easily maintained non-human primate model of this disorder.
We induced IDDM in 11 juvenile cynomolgus monkeys after a single (150 mg/kg) intravenous injection of streptozotocin (STZ). All diabetic monkeys were treated with insulin twice daily, based on a sliding scale. Subcutaneous vascular access ports were surgically placed in each monkey to facilitate serial blood sampling and drug administration. Allogeneic pancreatic islet cells from unrelated donors were subsequently transplanted into the mesenteric circulation of all STZ-treated monkeys.
Mild, transient nausea and vomiting occurred in all animals after STZ injection; however, no additional signs of toxicity occurred. Within 36 hr, all monkeys required twice daily administration of exogenous insulin to maintain a non-ketotic state. Serum C-peptide levels decreased from >1.2 ng/ml before STZ, to between 0.0 and 0.9 ng/ml after STZ, confirming islet cell destruction. Animals were maintained in an insulin-dependent state for up to 147 days without any observable clinical complications. Subcutaneous vascular access port patency was maintained up to 136 days with a single incidence of local infection. Islet cell transplantation resulted in normoglycemia within 24 hr. Serum C-peptide levels increased (range: 2-8 ng/ml) for 6 - 8 days in immune competent animals, and for 39-98 days after transplant in immunosuppressed monkeys.
IDDM can be consistently induced and safely treated in juvenile cynomolgus monkeys. Chronic vascular access can be maintained with minimal supervision and complications. This model is appropriate for studies investigating potential treatments for IDDM including islet cell transplantation.
胰岛素依赖型糖尿病（IDDM）是儿童中第二常见的慢性病。由于缺乏这种疾病可重复且易于维持的非人灵长类动物模型，阻碍了对IDDM治疗方法的研究。
我们对11只幼年食蟹猴单次静脉注射链脲佐菌素（STZ，150mg/kg）诱导IDDM。所有糖尿病猴根据血糖滑动标尺每天接受两次胰岛素治疗。通过手术在每只猴体内植入皮下血管通路端口，以方便连续采血和给药。随后将来自无关供体的同种异体胰岛细胞移植到所有接受STZ治疗的猴的肠系膜循环中。
注射STZ后所有动物均出现轻度、短暂的恶心和呕吐；然而，未出现其他毒性迹象。在36小时内，所有猴都需要每天两次注射外源性胰岛素以维持非酮症状态。血清C肽水平从STZ注射前的>1.2ng/ml降至注射后0.0至0.9ng/ml之间，证实胰岛细胞被破坏。动物在胰岛素依赖状态下维持长达147天，无任何可观察到的临床并发症。皮下血管通路端口通畅维持长达136天，仅发生一次局部感染。胰岛细胞移植在24小时内导致血糖正常。免疫功能正常的动物血清C肽水平在6 - 8天内升高（范围：2 - 8ng/ml），免疫抑制的猴在移植后39 - 98天升高。
在幼年食蟹猴中可以持续诱导并安全治疗IDDM。慢性血管通路可以在最少的监督和并发症情况下维持。该模型适用于研究IDDM的潜在治疗方法，包括胰岛细胞移植。
