Johnson K H, O'Brien T D, Hayden D W, Jordan K, Ghobrial H K, Mahoney W C, Westermark P
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Minnesota, St. Paul 55108.
Am J Pathol. 1988 Jan;130(1):1-8.
A novel putative polypeptide hormone identified as islet amyloid polypeptide (IAPP) was recently purified from islet amyloid (IA) of diabetic humans and cats, and also from amyloid of a human insulinoma. Although the function of IAPP is yet unknown, its occurrence in pancreatic endocrine tissue and its partial amino acid sequence identity with calcitonin gene-related peptide (CGRP) suggests an endocrine regulatory effect. In the present investigation, the authors utilized antisera to insulin, glucagon, somatostatin, pancreatic polypeptide, synthetic human CGRP, and a synthetic human IAPP (7-17) undecapeptide to immunohistochemically (PAP technique) document the presence of IAPP immunoreactive cells in the islets of the cat, dog, mouse, and rat, but not in the islets of the horse or calf. In serial sections of islets from these species it was shown that IAPP immunoreactivity occurred in insulin-reactive beta cells. This observation was confirmed immunocytochemically in cat islets by means of protein A-gold probes. With protein A-gold labeling techniques, IAPP immunoreactivity was localized to the outer lucent compartment of the beta cell secretory granule, whereas insulin immunoreactivity was associated with the electron-dense core. These findings provide strong evidence that IAPP or an IAPP precursor is synthesized by beta cells and is stored in beta cell granules for subsequent co-secretion with insulin. The conservation of IAPP in humans and multiple animal species and the localization of IAPP to pancreatic beta cells provide further evidence that IAPP has an important endocrine regulatory function. The propensity of IAPP to polymerize and form IA fibrils in diabetes associated with aging may indicate that IAPP is in some way also linked to the development of Type 2 diabetes.
一种新的假定多肽激素被鉴定为胰岛淀粉样多肽（IAPP），最近从糖尿病患者和猫的胰岛淀粉样物（IA）以及人类胰岛素瘤的淀粉样物中纯化得到。尽管IAPP的功能尚不清楚，但其在胰腺内分泌组织中的存在以及与降钙素基因相关肽（CGRP）的部分氨基酸序列同源性提示其具有内分泌调节作用。在本研究中，作者利用抗胰岛素、胰高血糖素、生长抑素、胰多肽、合成人CGRP以及合成人IAPP（7-17）十一肽的抗血清，通过免疫组织化学（PAP技术）证实了猫、狗、小鼠和大鼠胰岛中存在IAPP免疫反应性细胞，但马或小牛的胰岛中不存在。在这些物种胰岛的连续切片中显示，IAPP免疫反应性出现在胰岛素反应性β细胞中。这一观察结果通过蛋白A-金探针在猫胰岛中得到免疫细胞化学证实。采用蛋白A-金标记技术，IAPP免疫反应性定位于β细胞分泌颗粒的外层透明区，而胰岛素免疫反应性与电子致密核心相关。这些发现提供了强有力的证据，表明IAPP或IAPP前体由β细胞合成并储存在β细胞颗粒中，以便随后与胰岛素共同分泌。IAPP在人类和多种动物物种中的保守性以及IAPP在胰腺β细胞中的定位进一步证明IAPP具有重要的内分泌调节功能。IAPP在与衰老相关的糖尿病中聚合并形成IA纤维的倾向可能表明IAPP在某种程度上也与2型糖尿病的发生有关。
