Wang Xu, Yu Song, Gao Su-Jie, Hu Jiang-Ping, Wang Yue, Liu Hai-Xing
Neuro Endocrinol Lett. 2014;35(3):224-9.
Amyloid-beta (Abeta) is a 36-43 amino acid peptide that is derived by processing of the beta-amyloid precursor protein (APP). Abeta plays a central role in the development of Alzheimer's disease (AD). Although growing evidence suggests that insulin has important functions in Abeta metabolism, the underlying mechanisms are still unknown.
Using an SH-SY5Y cell line overexpressing human APP Swedish mutant (APPsw), we evaluated the effect of insulin on APP processing and Abeta production by using western blot analysist.
Our data showed that administration of insulin reduced the Abeta generation in culture media with a concomitant decreases in the levels of beta-secretase BACE1, secreted extracellular domain (sAPPbeta) and a fragment of 99 amino acids (C99) in APPsw cells. We further showed that insulin increased the levels of alpha-secretase ADAM10, a secreted extracellular domain secreted (sAPPa) and a fragment of 83 amino acids (C83) in APPsw cells.
Our present data suggest that insulin could inhibit Abeta production through modulation of APP processing by increasing cleavage at the a-secretase site and decreased cleavage at the beta-secretase sites.
β淀粉样蛋白（Aβ）是一种由β淀粉样前体蛋白（APP）加工产生的含36 - 43个氨基酸的肽段。Aβ在阿尔茨海默病（AD）的发展过程中起着核心作用。尽管越来越多的证据表明胰岛素在Aβ代谢中具有重要功能，但其潜在机制仍不清楚。
利用过表达人APP瑞典突变体（APPsw）的SH - SY5Y细胞系，通过蛋白质免疫印迹分析评估胰岛素对APP加工和Aβ产生的影响。
我们的数据显示，给予胰岛素可减少培养基中Aβ的生成，同时APPsw细胞中β分泌酶BACE1、分泌型细胞外结构域（sAPPβ）和99个氨基酸片段（C99）的水平也随之降低。我们进一步表明，胰岛素可增加APPsw细胞中α分泌酶ADAM10、分泌型细胞外结构域（sAPPα）和83个氨基酸片段（C83）的水平。
我们目前的数据表明，胰岛素可通过调节APP加工过程，增加α分泌酶位点的切割并减少β分泌酶位点的切割，从而抑制Aβ的产生。
