Rees D A, Alcolado J C
Department of Medicine, University of Wales College of Medicine, Cardiff, UK.
Diabet Med. 2005 Apr;22(4):359-70. doi: 10.1111/j.1464-5491.2005.01499.x.
Animal models have been used extensively in diabetes research. Early studies used pancreatectomised dogs to confirm the central role of the pancreas in glucose homeostasis, culminating in the discovery and purification of insulin. Today, animal experimentation is contentious and subject to legal and ethical restrictions that vary throughout the world. Most experiments are carried out on rodents, although some studies are still performed on larger animals. Several toxins, including streptozotocin and alloxan, induce hyperglycaemia in rats and mice. Selective inbreeding has produced several strains of animal that are considered reasonable models of Type 1 diabetes, Type 2 diabetes and related phenotypes such as obesity and insulin resistance. Apart from their use in studying the pathogenesis of the disease and its complications, all new treatments for diabetes, including islet cell transplantation and preventative strategies, are initially investigated in animals. In recent years, molecular biological techniques have produced a large number of new animal models for the study of diabetes, including knock-in, generalized knock-out and tissue-specific knockout mice.
动物模型在糖尿病研究中得到了广泛应用。早期研究使用胰腺切除的狗来证实胰腺在葡萄糖稳态中的核心作用,最终促成了胰岛素的发现与提纯。如今,动物实验颇具争议,且受到世界各地不同的法律和伦理限制。大多数实验是在啮齿动物身上进行的,不过仍有一些研究在较大型动物身上开展。包括链脲佐菌素和四氧嘧啶在内的几种毒素可在大鼠和小鼠中诱发高血糖症。选择性近亲繁殖培育出了几种动物品系,它们被视为1型糖尿病、2型糖尿病以及肥胖和胰岛素抵抗等相关表型的合理模型。除了用于研究疾病的发病机制及其并发症外,所有糖尿病的新疗法,包括胰岛细胞移植和预防策略,最初都是在动物身上进行研究的。近年来,分子生物学技术催生了大量用于糖尿病研究的新动物模型,包括基因敲入、全身性基因敲除和组织特异性基因敲除小鼠。