AMYLOID FIBRILS IN HUMAN INSULINOMA AND ISLETS OF LANGERHANS OF THE DIABETIC CAT ARE DERIVED FROM A NEUROPEPTIDE-LIKE PROTEIN ALSO PRESENT IN NORMAL ISLET CELLS
AMYLOID FIBRILS IN HUMAN INSULINOMA AND ISLETS OF LANGERHANS OF THE DIABETIC CAT ARE DERIVED FROM A NEUROPEPTIDE-LIKE PROTEIN ALSO PRESENT IN NORMAL ISLET CELLS
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DOI：
10.1073/pnas.84.11.3881
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发表时间：
1987-06-01
影响因子：
11.1
通讯作者：
JOHNSON, KH
中科院分区：
文献类型：
--
作者：
WESTERMARK, P;WERNSTEDT, C;JOHNSON, KH
定位于朗格汉斯胰岛的淀粉样蛋白沉积是非胰岛素依赖型人类糖尿病和成年猫糖尿病的典型表现。淀粉样蛋白沉积也常见于产生胰岛素的胰腺肿瘤。我们从人和猫的胰岛淀粉样蛋白以及人胰岛素瘤的淀粉样蛋白中提纯了一种主要的蛋白质。胰岛素瘤或胰岛淀粉样多肽(IAPP)。人胰岛素瘤IAPP含有37个氨基酸残基，理论相对分子质量为3850Da。氨基酸序列是独一无二的，但与人类降钙素基因相关肽有40%的同源性。人胰岛素瘤IAPP的第1-27位猫胰岛IAPP的部分氨基酸序列与人IAPP完全相同，但有3个位置发生了替换。人工合成的人胰岛素瘤IAPP-(7-17)十一肽的抗血清与人和猫胰岛淀粉样蛋白以及胰岛B细胞具有特异的免疫组织化学反应。这种胰腺神经肽样蛋白的意义尚不清楚，但它可能发挥重要的内分泌调节作用。
Amyloid deposits localized to the islets of Langerhans are typical of non-insulin-dependent human diabetes mellitus and of diabetes mellitus in adult cats. Amyloid deposits also commonly occur in insulin-producing pancreatic tumors. We have purified a major protein.sbd.insulinoma or islet amyloid polypeptide (IAPP).sbd.from human and cat islet amyloid and from amyloid of a human insulinoma. IAPP from human insulinoma contained 37 amino acid residues and had a theoretical molecular mass of 3850 Da. The amino acid sequence is unique but has > 40% identity with the human calcitonin gene-related peptide. A partial amino acid sequence of cat islet IAPP corresponding to positions 1-27 of human insulinoma IAPP was identical to the human IAPP except for substitutions in three positions. An antiserum raised to a synthetic human insulinoma IAPP-(7-17) undecapeptide showed specific immunohistochemical reactivity with human and cat islet amyloid and with islet B cells. The significance of this pancreatic neuropeptide-like protein is unknown, but it is suggested that it may exert an important endocrine regulatory effect.