ABSTRACT

A rapid-acting insulin lispro and long-acting insulin glargine are commonly used for the treatment of diabetes. Clinical cases have described the formation of injectable amyloidosis with these insulin analogues, but their amyloid core regions of fibrils were unknown. To reveal these regions, we have analysed the hydrolyzates of insulin fibrils and its analogues using high-performance liquid chromatography and mass spectrometry methods and found that insulin and its analogues have almost identical amyloid core regions that intersect with the predicted amyloidogenic regions. The obtained results can be used to create new insulin analogues with a low ability to form fibrils.

Abbreviations

a.a., amino acid residues; HPLC-MS, high-performance liquid chromatography/mass spectrometry; m/z, mass-to-charge ratio; TEM, transmission electron microscopy.

中文翻译：

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胰岛素类似物原纤维淀粉样蛋白核心区的测定。

摘要

速效赖脯胰岛素和长效甘精胰岛素常用于治疗糖尿病。临床病例描述了用这些胰岛素类似物形成可注射的淀粉样变性，但它们的原纤维淀粉样蛋白核心区域是未知的。为了揭示这些区域，我们使用高效液相色谱法和质谱法分析了胰岛素原纤维及其类似物的水解产物，发现胰岛素及其类似物具有几乎相同的淀粉样蛋白核心区域，与预测的淀粉样蛋白生成区域相交。所获得的结果可用于创建具有低形成原纤维能力的新胰岛素类似物。

缩写

aa，氨基酸残基；HPLC-MS、高效液相色谱/质谱；m/z，质荷比；TEM，透射电子显微镜。