SEQUENCE DIVERGENCE IN A SPECIFIC REGION OF ISLET AMYLOID POLYPEPTIDE (IAPP) EXPLAINS DIFFERENCES IN ISLET AMYLOID FORMATION BETWEEN SPECIES
SEQUENCE DIVERGENCE IN A SPECIFIC REGION OF ISLET AMYLOID POLYPEPTIDE (IAPP) EXPLAINS DIFFERENCES IN ISLET AMYLOID FORMATION BETWEEN SPECIES
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DOI：
10.1016/0014-5793(89)81467-x
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发表时间：
1989-07-17
期刊：
影响因子：
3.5
通讯作者：
WESTERMARK, P
中科院分区：
文献类型：
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作者：
BETSHOLTZ, C;CHRISTMANSSON, L;WESTERMARK, P
郎格汉斯胰岛中的淀粉样沉积与人类和猫的2型糖尿病(DM)有关，由一种称为胰岛淀粉样多肽(IAPP)的37个氨基酸组成。为了解释胰岛淀粉样蛋白(IA)在常见啮齿动物中不发育的情况，我们推导了IAPP分子在小鼠、大鼠和仓鼠中的氨基酸序列。我们发现分子的一个特定区域在很大程度上发散。与人和仓鼠IAPP的这一区域相对应的合成肽在体外比较了它们形成淀粉样纤维的能力。人肽很容易形成具有淀粉样蛋白特征的纤维，而仓鼠多肽则完全缺乏这种特性。我们认为这可能是人类和啮齿动物之间IA形成差异的一个可能的解释，并讨论了我们在2型DM综合征方面的发现。
Amyloid deposits in the islets of Langerhans occur in association with type 2 diabetes mellitus (DM) in humans and cats and consist of a 37‐amino‐acid polypeptide known as islet amyloid polypeptide (IAPP). In order to find an explanation for the situation that islet amyloid (IA) does not develop in common rodent species, we have deduced the amino acid sequence of the IAPP molecule in mouse, rat and hamster. We find that a specific region of the molecule diverges to a high degree. Synthetic peptides corresponding to this region of human and hamster IAPP were compared for their ability to form amyloid fibrils in vitro. Whereas the human peptide readily formed fibrils with amyloid character, the hamster peptide completely lacked this property. We suggest this to be a likely explanation for the differences in IA formation between humans and rodents and discuss our findings in relation to the type 2 DM syndrome.