Pathophysiological Significance of IAPP in NIDDM

胰岛淀粉样多肽(IAPP/Amylin)是一种由37个氨基酸组成的多肽，是非胰岛素依赖型糖尿病(NIDDM)和胰岛素瘤中胰岛淀粉样蛋白的主要成分。为了探讨IAPP在NIDDM中的病理生理意义，我们研究了IAPP在糖尿病患者和糖尿病大鼠模型中的组织含量、血浆水平、基因表达、对生理刺激的反应以及IAPP的免疫组化定位。我们还阐明了形成胰腺淀粉样蛋白的哺乳动物(人和猫)和不形成胰腺淀粉样蛋白的哺乳动物(大鼠和小鼠)的胰腺、胃肠道和血浆中该肽的分子形式。13个胰岛素瘤中有11个对IAPP和胰岛素都有免疫反应，但另外两个只有胰岛素免疫反应。在5例胰岛素瘤中发现淀粉样物沉积，其临床特征将被公布。此外，我们还报道了NIDDM中淀粉样蛋白和胃泌素瘤中淀粉样蛋白的病理特征。胰岛淀粉样蛋白沉积可能是胰岛功能紊乱的继发性表现，但我们不能排除淀粉样蛋白沉积加剧了胰岛功能障碍，并可能参与了NIDDM的进展。

Islet amyloid polypeptide(IAPP/amylin) is a 37 amino acid long peptide, being a major component of islet amyloid in non-insulin-dependent diabetes mellitus(NIDDM) and insulinoma. To delineate the pathophysiological significance of IAPP in NIDDM, we studied tissue content, plasma level, gene expression, response to physiological stimulation and immunohistochemical localization of the peptide in diabetics and rat models of diabetes. We also clarified molecular forms of the peptide in the pancreas, gastrointestinal tract and plasma from mammals that form pancreatic amyloid(human and cat) and mammals that do not form it(rat and mouse). Eleven of thirteen insulinomas had both immunoreactivities for IAPP and insulin, but other two had only insulin-immunoreactivity. Amyloid deposits were noted in 5 insulinomas whose clinical features will be presented. In addition, we report pathological features of amyloid in NIDDM and the amyloid in a gastrinoma. Islet amyloid deposition might be a secondary manifestation of disordered islet function, although we can not exclude that amyloid deposits intensify islet dysfunction and may contribute to the progression of NIDDM.