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Goettingen Minipigs (GMP): Comparison of Two Different Models for Inducing Diabetes

机译:哥廷根小型猪(GMP):两种不同模型诱导糖尿病的比较

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Purpose Preclinical experiments on large animals are indispensable for evaluating the effectiveness of diabetes therapies. Miniature swine are well suited for such studies due to their physiological and pathophysiological responses. Methods We compare two methods for inducing diabetes in Goettingen minipigs (GMP), in five with the beta cell toxin streptozotocin (STZ) and in five other GMP by total pancreatectomy (PE). Glucose homeostasis was assessed with the intravenous glucose-tolerance test (IVGTT) and continual monitoring of interstitial glucose levels. At conclusion of the observation period, the pancreata were examined histologically. Three non-diabetic GMP served as control group. Results The IVGTT revealed markedly diabetic profiles in both GMP groups. STZ-GMP were found to harbor residual C-peptides and scattered insulin-positive cells in the pancreas. PE-GMP survived the total pancreatectomy only with intensive postoperative care. Conclusions Although both methods reliably induced diabetes in GMP, the PE-GMP clearly had more health problems and required a greater expenditure of time and resources. The PE-GMP model, however, was better at eliminating endogenous insulin and C-peptide than the STZ-GMP model.
机译:目的对大型动物进行临床前实验对于评估糖尿病治疗的有效性必不可少。小型猪由于其生理和病理生理反应而非常适合此类研究。方法我们比较了两种在Goettingen小型猪(GMP)中诱导糖尿病的方法,其中五种采用β细胞毒素链脲佐菌素(STZ),另外五种采用全胰切除术(PE)诱导糖尿病。通过静脉葡萄糖耐量试验(IVGTT)和间质葡萄糖水平的持续监测来评估葡萄糖稳态。在观察期结束时,对胰腺进行组织学检查。以三个非糖尿病GMP为对照组。结果IVGTT显示两组GMP均具有明显的糖尿病特征。发现STZ-GMP在胰腺中带有残留的C肽和散布的胰岛素阳性细胞。 PE-GMP仅在术后加强监护下才能在全胰腺切除术中幸存。结论尽管这两种方法均能可靠地诱发GMP中的糖尿病,但PE-GMP显然存在更多的健康问题,并且需要花费更多的时间和资源。然而,PE-GMP模型在消除内源性胰岛素和C肽方面比STZ-GMP模型更好。

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