Amylin (islet amyloid polypeptide [IAPP]) is a neuroendocrine hormone synthesized with insulin in the beta cells of pancreatic islets. The two hormones act in different ways: in fact insulin triggers glucose uptake in muscle and liver cells, removing glucose from the bloodstream and making it available for energy use and storage, while amylin regulates glucose homeostasis. Aside these positive physiological aspects, human amyloid polypeptide (hIAPP) readily forms amyloid in vitro. Amyloids are aggregates of proteins and in the human body amyloids are considered responsible of the development of various diseases. These aspects have been widely described and discussed in literature and to give a view of the highly complexity of this biochemical behavior the different physical, chemical, biological and medical aspects are shortly described in this review. It is strongly affected by the presence on metal ions, responsible for or inhibiting the formation of fibrils. Mass spectrometry resulted (and still results) to be a particularly powerful tool to obtain valid and effective experimental data to describe the hIAPP behavior. Aside classical approaches devoted to investigation on metal ion-hIAPP structures, which reflects on the identification of metal–protein interaction site(s) and of possible metal-induced conformational changes of the protein, interesting results have been obtained by ion mobility mass spectrometry, giving, on the basis of collisional cross-section data, information on both the oligomerization processes and the conformation changes. Laser ablation electrospray ionization—ion mobility spectrometry-mass spectrometry (LAESI-IMS-MS), allowed to obtain information on the binding stoichiometry, complex dissociation constant, and the oxidation state of the copper for the amylin–copper interaction. Alternatively to inorganic ions, small organic molecules have been tested by ESI-IMS-MS as inhibitor of amyloid assembly. Also in this case the obtained data demonstrate the validity of the ESI-IMS-MS approach as a high-throughput screen for inhibitors of amyloid assembly, providing valid information concerning the identity of the interacting species, the nature of binding and the effect of the ligand on protein aggregation. Effects of Cu²⁺ and Zn²⁺ ions in the degradation of human and murine IAPP by insulin-degrading enzyme were studied by liquid chromatography/mass spectrometry (LC/MS). The literature data show that mass spectrometry is a highly valid and effective tool in the study of the amylin behavior, so to individuate medical strategies to avoid the undesired formation of amyloids in in vivo conditions.

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质谱在胰淀素与金属离子相互作用研究中的作用

胰淀素（胰岛淀粉样多肽 [IAPP]）是一种在胰岛 β 细胞中与胰岛素合成的神经内分泌激素。这两种激素以不同的方式起作用：事实上，胰岛素会触发肌肉和肝细胞中的葡萄糖摄取，从血液中去除葡萄糖并使其可用于能量使用和储存，而胰淀素调节葡萄糖稳态。除了这些积极的生理方面，人淀粉样蛋白多肽 (hIAPP) 很容易在体外形成淀粉样蛋白. 淀粉样蛋白是蛋白质的聚集体，在人体内，淀粉样蛋白被认为是导致各种疾病发展的原因。这些方面已在文献中得到广泛描述和讨论，为了了解这种生化行为的高度复杂性，本综述简要描述了不同的物理、化学、生物学和医学方面。它受金属离子的存在的强烈影响，金属离子负责或抑制原纤维的形成。质谱法导致（并且仍然是结果）成为一种特别强大的工具，可以获取有效的实验数据来描述 hIAPP 行为。除了致力于研究金属离子-hIAPP 结构的经典方法外，这反映了金属-蛋白质相互作用位点的鉴定和可能的金属诱导的蛋白质构象变化，通过离子淌度质谱法获得了有趣的结果，在碰撞截面数据的基础上，给出了信息关于低聚过程和构象变化。激光烧蚀电喷雾电离-离子迁移率光谱-质谱法 (LAESI-IMS-MS)，可以获得有关胰岛淀粉样多肽-铜相互作用的结合化学计量、复合解离常数和铜的氧化态的信息。除了无机离子，小的有机分子已经通过 ESI-IMS-MS 测试作为淀粉样蛋白组装的抑制剂。同样在这种情况下，获得的数据证明了 ESI-IMS-MS 方法作为淀粉样蛋白组装抑制剂的高通量筛选的有效性，提供了有关相互作用物种的身份、结合的性质和作用的有效信息。蛋白质聚集上的配体。铜的影响通过液相色谱/质谱法 (LC/MS) 研究了胰岛素降解酶降解人和小鼠 IAPP 过程中的²⁺和 Zn ^2+离子。文献数据表明，质谱法是研究胰岛淀粉样多肽行为的一种高度有效的工具，因此可以制定个体化的医疗策略，以避免在体内条件下形成不需要的淀粉样蛋白。