Seita Masayuki, Noguchi Hirofumi, Kubota Yasuhiro, Kawamoto Hironobu, Nakaji Shuhei, Kobayashi Naoya, Fujiwara Toshiyoshi
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan.
† Department of Surgery, Clinical Research Center, Chiba-East National Hospital, National Hospital Organization , Chiba , Japan.
Cell Med. 2013 Oct 21;6(1-2):25-31. doi: 10.3727/215517913X674289. eCollection 2013 Dec 30.
We created canine models of type 1 diabetes that were suitable for the assessment of cell therapies, such as islet transplantation and bioartificial pancreas, with low-dose streptozotocin (STZ) injection and partial pancreatectomy. In our model, a 50% pancreatectomy was performed with general anesthesia, followed by systemic injection of 35 mg/kg STZ into a vein of the foreleg. Four weeks after the administration of STZ, the fasting blood glucose level of our model dogs was found to be over 200 mg/dl twice on different days, and we could not detect any canine insulin by the intravenous glucose tolerance test (IVGTT). We therefore diagnosed the dogs to have induced diabetes. Some studies have reported high-dose STZ to be very toxic for both the kidney and liver, and therefore a lower dose is desirable to induce diabetic models without any associated kidney or liver damage. We think that the combination of a partial pancreatectomy can thus make it possible to reduce the dose of STZ, and it is therefore useful for the creation of type 1 diabetes models. We believe that our model is a safe and reliable model for type 1 diabetes in canines to assess the efficacy of pancreas-targeted cell therapies.
我们通过低剂量链脲佐菌素（STZ）注射和部分胰腺切除术，创建了适用于评估细胞疗法（如胰岛移植和生物人工胰腺）的1型糖尿病犬模型。在我们的模型中，在全身麻醉下进行50%的胰腺切除术，然后将35 mg/kg的STZ静脉注射到前腿静脉中。在注射STZ四周后，我们模型犬的空腹血糖水平在不同日期两次超过200 mg/dl，并且通过静脉葡萄糖耐量试验（IVGTT）检测不到任何犬胰岛素。因此，我们诊断这些犬患有诱导性糖尿病。一些研究报告称高剂量STZ对肾脏和肝脏都有很大毒性，因此较低剂量更适合用于诱导糖尿病模型而不造成任何相关的肾脏或肝脏损伤。我们认为部分胰腺切除术的联合使用因此可以降低STZ的剂量，所以它对于创建1型糖尿病模型很有用。我们相信我们的模型是一个安全可靠的犬1型糖尿病模型，可用于评估胰腺靶向细胞疗法的疗效。
