Institute of Clinical Biochemistry, Hannover Medical School, 30623, Hannover, Germany.
Diabetologia. 2014 Mar;57(3):512-21. doi: 10.1007/s00125-013-3125-4. Epub 2013 Dec 6.
AIMS/HYPOTHESIS: Research on the pathogenesis of type 1 diabetes relies heavily on good animal models. The aim of this work was to study the translational value of animal models of type 1 diabetes to the human situation.
We compared the four major animal models of spontaneous type 1 diabetes, namely the NOD mouse, BioBreeding (BB) rat, Komeda rat and LEW.1AR1-iddm rat, by examining the immunohistochemistry and in situ RT-PCR of immune cell infiltrate and cytokine pattern in pancreatic islets, and by comparing findings with human data.
After type 1 diabetes manifestation CD8(+) T cells, CD68(+) macrophages and CD4(+) T cells were observed as the main immune cell types with declining frequency, in infiltrated islets of all diabetic pancreases. IL-1β and TNF-α were the main proinflammatory cytokines in the immune cell infiltrate in NOD mice, BB rats and LEW.1AR1-iddm rats, as well as in humans. The Komeda rat was the exception, with IFN-γ and TNF-α being the main cytokines. In addition, IL-17 and IL-6 and the anti-inflammatory cytokines IL-4, IL-10 and IL-13 were found in some infiltrating immune cells. Apoptotic as well as proliferating beta cells were observed in infiltrated islets. In healthy pancreases no proinflammatory cytokine expression was observed.
CONCLUSIONS/INTERPRETATION: With the exception of the Komeda rat, the animal models mirror very well the situation in humans with type 1 diabetes. Thus animal models of type 1 diabetes can provide meaningful information on the disease processes in the pancreas of patients with type 1 diabetes.
目的/假设：1 型糖尿病发病机制的研究严重依赖于良好的动物模型。本研究旨在探讨 1 型糖尿病动物模型对人类情况的转化价值。
我们通过比较四种主要的自发性 1 型糖尿病动物模型，即 NOD 小鼠、BioBreeding（BB）大鼠、Komeda 大鼠和 LEW.1AR1-iddm 大鼠，检查胰岛内免疫细胞浸润和细胞因子模式的免疫组织化学和原位 RT-PCR，并将研究结果与人类数据进行比较。
在 1 型糖尿病发病后，CD8(+)T 细胞、CD68(+)巨噬细胞和 CD4(+)T 细胞被观察到是浸润胰岛中主要的免疫细胞类型，其频率逐渐下降。在 NOD 小鼠、BB 大鼠和 LEW.1AR1-iddm 大鼠以及人类的胰岛浸润免疫细胞中，IL-1β 和 TNF-α 是主要的促炎细胞因子。Komeda 大鼠是个例外，IFN-γ 和 TNF-α 是主要的细胞因子。此外，在一些浸润的免疫细胞中还发现了 IL-17 和 IL-6 以及抗炎细胞因子 IL-4、IL-10 和 IL-13。在浸润的胰岛中观察到凋亡和增殖的β细胞。在健康的胰腺中未观察到促炎细胞因子的表达。
结论/解释：除了 Komeda 大鼠外，这些动物模型非常好地反映了人类 1 型糖尿病的情况。因此，1 型糖尿病动物模型可以为 1 型糖尿病患者胰腺中的疾病过程提供有意义的信息。
