Development of a porcine model of type 1 diabetes by total pancreatectomy and establishment of a glucose tolerance evaluation method
Development of a porcine model of type 1 diabetes by total pancreatectomy and establishment of a glucose tolerance evaluation method
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DOI：
10.1111/j.1525-1594.2004.00002.x
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发表时间：
2004-11-01
影响因子：
2.4
通讯作者：
Tanaka, N
中科院分区：
文献类型：
--
作者：
Kobayashi, K;Kobayashi, N;Tanaka, N
目的：为了开发和评估人类糖尿病靶向细胞疗法的功效，非常需要在大型动物中建立可靠的模型。本文报道猪全胰切除术的手术技术以及全胰切除猪特征的生化分析。方法：对23头猪进行了全胰腺切除术。通过检查血糖、胰岛素、生物化学、活动指数和静脉葡萄糖耐量试验（IVGTT）来评估糖尿病猪的病理生理学特征。结果：共有 14 头猪成功接受了全胰腺切除术，无需胆道重建，并在本研究中进行了分析。活动指数从第 5 天开始下降，完全切除胰腺的猪的平均存活期为 7.6 +/- 2.7 天。在这些猪中没有证实内源性胰岛素分泌。接受全胰腺切除术的猪的酮体水平显着升高。全胰腺切除术后 4 天内进行的 IVGTT 显示，尽管没有内源性胰岛素分泌，但血糖水平自发下降。第 5 天或之后的 IVGTT 显示全胰腺切除术猪持续高血糖。组织学检查显示肝细胞萎缩，肝脏中糖原储存减少，小肠粘液产生减少。结论：本文描述了通过全胰腺切除术创建的猪糖尿病模型，并分析了动物的病理生理学特征。本研究表明，全胰腺切除术后第 5 天或之后进行 IVGTT 是评估细胞疗法疗效的可靠方法。
Purpose: To develop and evaluate the efficacy of diabetes-targeted cell therapies in humans, a reliable model in larger animals is highly desirable. This article reports the surgical technique of total pancreatectomy in pigs and the biochemical analysis of the characteristics of totally pancreatectomized pigs. Methods: Surgical total pancreatectomy was conducted in 23 pigs. Blood glucose, insulin, biochemistries, activity index, and intravenous glucose tolerance test (IVGTT) were examined to assess the pathophysiological profiles of diabetic pigs. Results: A total of 14 pigs successfully underwent total pancreatectomy without requiring biliary reconstruction and were analyzed in the present study. Activity index was decreased from day 5 on and the mean survival of totally pancreatectomized pigs was 7.6 +/- 2.7 days. No endogenous insulin secretion was confirmed in these pigs. Pigs which received total pancreatectomy demonstrated significantly higher levels of ketone bodies. IVGTT performed within 4 days after total pancreatectomy showed a spontaneous decrease in blood glucose levels despite an absence of endogenous insulin secretion. IVGTT on day 5 or later showed continued hyperglycemia in pigs with total pancreatectomy. Histological examination showed atrophy of hepatocytes and decreased glycogen storage in the liver and decreased mucus production of the small intestine. Conclusion: This article describes a porcine model of diabetes created by total pancreatectomy and it analyzes the pathophysiological profiles in the animals. The present study has suggested that IVGTT on day 5 or later after total pancreatectomy is a reliable method to evaluate the efficacy of cell therapies.