Insulin is a kinetic but not a thermodynamic inhibitor of amylin aggregation
Insulin is a kinetic but not a thermodynamic inhibitor of amylin aggregation
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胰岛素是胰淀素聚集的动力学抑制剂，但不是热力学抑制剂
DOI：
10.1111/j.1742-4658.2009.07061.x
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发表时间：
2009-06-01
期刊：
影响因子：
5.4
通讯作者：
Li, Yan-mei
中科院分区：
文献类型：
--
作者：
Cui, Wei;Ma, Jing-wen;Li, Yan-mei
2型糖尿病最重要的病理特征之一是胰岛淀粉样蛋白的形成，其主要成分是胰淀素肽。然而，天然抑制剂如胰岛素的存在可使胰淀素在健康个体中保持稳定和生理功能。一些先前的研究表明，胰岛素是一个有效的抑制胰淀素纤维形成在体外，但其他人得到了矛盾的结果。 因此，有必要阐明胰岛素对胰淀素聚集的影响。在这里，我们报告胰岛素是胰淀素聚集的动力学抑制剂，仅在有限的时间内保持其抑制作用。实际上，胰岛素在长期孵育后促进胰淀素聚集。此外，我们发现这种促进作用可以归因于胰岛素和胰淀素的共聚。我们还发现胰岛素与胰淀素单体或低聚物共聚，而不是预先形成的胰淀素原纤维。这些结果表明，胰岛素和胰淀素之间的相互作用可能不仅有助于抑制胰淀素聚集，而且有助于2型糖尿病中两种肽的共聚集。
One of the most important pathological features of type 2 diabetes is the formation of islet amyloid, of which the major component is amylin peptide. However, the presence of a natural inhibitor such as insulin may keep amylin stable and physiologically functional in healthy individuals. Some previous studies demonstrated that insulin was a potent inhibitor of amylin fibril formation in vitro, but others obtained contradictory results. Hence, it is necessary to elucidate the effects of insulin on amylin aggregation. Here we report that insulin is a kinetic inhibitor of amylin aggregation, only keeping its inhibitory effect for a limited time period. Actually, insulin promotes amylin aggregation after long‐term incubation. Furthermore, we found that this promotional effect could be attributed to the copolymerization of insulin and amylin. We also found that insulin copolymerized with amylin monomer or oligomer rather than preformed amylin fibrils. These results suggest that the interaction between insulin and amylin may contribute not only to the inhibition of amylin aggregation but also to the coaggregation of both peptides in type 2 diabetes.