The polypeptide amylin is responsible for islet amyloid in type 2 diabetes, a process which contributes to β-cell death in the disease. The role of the N-terminal region of amylin in amyloid formation is relatively unexplored, although removal of the disulfide bridged loop between Cys-2 and Cys-7 accelerates amyloid formation. We examine the des Lys-1 variant of human amylin (h-amylin), a variant which is likely produced in vivo. Lys-1 is a region of high charge density in the h-amylin amyloid fiber. The des Lys-1 polypeptide forms amyloid on the same time scale as wild-type amylin in phosphate buffered saline, but does so more rapidly in Tris. The des Lys-1 variant is somewhat less toxic to cultured INS cells than wild type. The implications for the in vitro mechanism of amyloid formation and for comparative analysis of amyloidogenicity are discussed.

中文翻译：

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des-Lys-1 人胰淀素的淀粉样变性和细胞毒性提供了对胰淀素自组装的深入了解，并强调了定义淀粉样变性的困难。


多肽胰淀素负责 2 型糖尿病中胰岛淀粉样蛋白的形成，这一过程会导致该疾病中的 β 细胞死亡。尽管去除 Cys-2 和 Cys-7 之间的二硫桥环会加速淀粉样蛋白的形成，但胰淀素 N 端区域在淀粉样蛋白形成中的作用相对尚未被探索。我们检查了人胰岛淀粉样多肽（h-amylin）的 des Lys-1 变体，这是一种可能在体内产生的变体。 Lys-1 是 h-amylin 淀粉样纤维中的高电荷密度区域。 des Lys-1 多肽在磷酸盐缓冲盐水中与野生型胰岛淀粉样多肽形成淀粉样蛋白的时间尺度相同，但在 Tris 中形成淀粉样蛋白的速度更快。 des Lys-1 变体对培养的 INS 细胞的毒性比野生型稍低。讨论了淀粉样蛋白形成的体外机制和淀粉样蛋白生成性的比较分析的含义。