Larsen Marianne O, Rolin Bidda
Department of Pharmacology Research I, Novo Nordisk A/S, Maaloev, Denmark.
ILAR J. 2004;45(3):303-13. doi: 10.1093/ilar.45.3.303.
Animal models of type 1 diabetes remain essential tools for investigation of the etiology and pathogenesis of the disease and, importantly, for the development of effective new treatments. Although a range of well-characterized and widely used models of type 1 diabetes in rodents are currently available, large animal models are a valuable complement to rodent models for both physiological and practical reasons. The pig is very useful in many aspects as a model for human physiology and pathophysiology because many organ systems of this species, as well as physiological and pathophysiological responses, resemble those of the human. The Göttingen minipig is particularly suitable for long-term studies because of its inherent small size and ease of handling, even at full maturity. Of particular relevance to the field of type 1 diabetes are the many similarities evident between humans and pigs with regard to pharmacokinetics of compounds after subcutaneous administration, structure and function of the gastrointestinal tract, morphology of the pancreas, and the overall metabolic status of the two species. Because spontaneous type 1-like diabetes is very rare in pigs, a model of the condition must be induced experimentally, either surgically or chemically. This process is discussed, and the use of the pig as a model in islet transplantation and diabetic complications is briefly summarized.
1型糖尿病动物模型仍然是研究该疾病病因和发病机制的重要工具,而且对于开发有效的新治疗方法也至关重要。尽管目前已有一系列特征明确且广泛应用的啮齿类动物1型糖尿病模型,但出于生理和实际原因,大型动物模型是啮齿类动物模型的宝贵补充。猪作为人类生理学和病理生理学模型在很多方面都非常有用,因为该物种的许多器官系统以及生理和病理生理反应都与人类相似。哥廷根小型猪因其固有的小体型和易于操作的特点,即使在完全成熟时也特别适合长期研究。与1型糖尿病领域特别相关的是,人类和猪在皮下给药后化合物的药代动力学、胃肠道的结构和功能、胰腺的形态以及这两个物种的整体代谢状态方面存在许多明显的相似之处。由于猪中自发性1型糖尿病样疾病非常罕见,因此必须通过手术或化学方法实验性诱导该疾病模型。本文将讨论这一过程,并简要总结猪在胰岛移植和糖尿病并发症中的模型应用。