胰岛淀粉样多肽的分子结构、毒性及其抑制因素

doi:10.3969/j.issn.2095-1396.2016.04.008

摘要/Abstract

摘要： 人胰岛淀粉样多肽（human amylin，hAmylin）是 2 型糖尿病患者胰岛中淀粉样蛋白沉积的主要成分，是由 37 个氨基酸组成的多肽。生理状态下，hAmylin 与胰岛素共同产生并储存于胰岛β细胞，按 1 ∶ 100 的比例共同分泌，且促进胰岛素分泌的因素亦均可促进 hAmylin 分泌。hAmylin 的单体结构未折叠，呈不稳定状态。与β淀粉样蛋白（amyloid β peptide，Aβ）一样，hAmylin 的细胞毒性与其单体状态不稳定，易发生聚集，形成寡聚物及纤维结构的特性有关。hAmylin 的聚集会对细胞造成不可逆的损伤。该文重点综述了 hAmylin 的结构、聚集与脂质膜的相互作用、毒性及其毒性抑制剂的最新研究进展。

关键词: 人胰岛淀粉样多肽, 2 型糖尿病, 分子结构, 细胞毒性

Abstract: Human amylin （hAmylin） is the major component of amyloid deposits in the pancreatic islets of patients with diabetes mellitus 2 （DM2）. Physiologically，mature hAmylin，a 37 amino acid peptide，is co-produced and co-secreted with insulin in a ratio of 1∶100 in islet β-cells. hAmylin is released in response to the stimuli that lead to insulin secretion. The monomeric hAmylin is an unstable and unfolded peptide which tends to accumulate and form oligomer or fibril. The unstable state of hAmylin monomer is closely related to hAmylin cytotoxicity. Accumulating evidences suggest that hAmylin amyloid accumulation that accompany DM2 is not just an insignificant phenomenon derived from the disease progression but that hAmylin aggregation induces processes that impair the functionality and the viability of β-cells. In this review，we particularly focus on hAmylin structure，hIAPP aggregation and hAmylin-membrane interactions. We will discuss recent findings on the mechanism of hAmylin-membrane damage and hIAPP-induced cell death. Finally，the development of successful anti-amyloidogenic agents that prevent hAmylin fibril formation have been discussed.

Key words: human amylin, diabetes mellitus 2, molecular structure, cytotoxicity

张楠，邢媛，张炜. 胰岛淀粉样多肽的分子结构、毒性及其抑制因素[J]. 神经药理学报, 2016, 6(4): 50-64.

ZHANG Nan，XING Yuan，ZHANG Wei. Molecular Structure，Cytotoxicity and Inhibitive Factors of Human Amylin[J]. Acta Neuropharmacologica, 2016, 6(4): 50-64.

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