Ma Z, Westermark G T, Johnson K H, O'Brien T D, Westermark P
Division of Molecular and Immunological Pathology, Faculty of Health Sciences, Linköping University, Sweden.
Amyloid. 1998 Dec;5(4):255-61. doi: 10.3109/13506129809007298.
Islet amyloid polypeptide (IAPP, "amylin") has been proposed as having important roles in the pathogenesis of type 2 diabetes mellitus via its biological activity and by forming islet amyloid. The domestic cat develops a type of diabetes that closely resembles type 2 diabetes in humans, including the frequent formation of islet amyloid deposits in the impaired glucose tolerant (IGT) and diabetic state. With the aid of computerized image analysis and immunohistochemistry, we examined the IAPP and insulin content in pancreatic islets of normal, IGT and diabetic cats. IAPP immunoreactivity in beta cells from IGT cats was significantly stronger (p < 0.01) as compared with cells from normal cats, while the insulin labelling strength was unchanged. Overtly diabetic cats were usually almost devoid of beta cells. As in humans, cellular IAPP but not IAPP in islet amyloid deposits was labelled by the newly developed monoclonal antibody to IAPP 4A5, thus providing further evidence that IAPP is modified by a yet unknown mechanism during the amyloidogenic process. The study provides evidence that an increased beta cell storage of IAPP independent of insulin may be an important factor in the early phase of the development of islet amyloid in this form of diabetes.
胰岛淀粉样多肽（IAPP，“胰淀素”）因其生物活性和形成胰岛淀粉样物质，被认为在2型糖尿病发病机制中发挥重要作用。家猫患有一种与人类2型糖尿病极为相似的糖尿病，包括在糖耐量受损（IGT）和糖尿病状态下频繁形成胰岛淀粉样沉积物。借助计算机图像分析和免疫组织化学技术，我们检测了正常、IGT和糖尿病猫胰岛中的IAPP和胰岛素含量。与正常猫的细胞相比，IGT猫β细胞中的IAPP免疫反应性显著增强（p < 0.01），而胰岛素标记强度未变。明显糖尿病的猫通常几乎没有β细胞。与人类一样，新开发的针对IAPP的单克隆抗体4A5标记的是细胞内的IAPP，而非胰岛淀粉样沉积物中的IAPP，从而进一步证明IAPP在淀粉样变过程中通过未知机制发生了修饰。该研究表明，在这种形式的糖尿病中，IAPP在β细胞中的储存增加且独立于胰岛素，可能是胰岛淀粉样变发展早期的一个重要因素。
