Overexpression of insulin degrading enzyme: Cellular localization and effects on insulin signaling

Overexpression of insulin degrading enzyme: Cellular localization and effects on insulin signaling
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DOI:
10.1006/bbrc.1997.6066
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发表时间:
1997-02-03
影响因子:
3.1
通讯作者:
Roth, RA
Roth, RA
中科院分区:
生物学4区
文献类型:
--
作者:
Seta, KA;Roth, RA

文献摘要

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为了研究胰岛素降解酶(胰岛素溶素,EC 3.4.24.56)在胰岛素信号传导中的作用,对过表达人胰岛素受体的中国仓鼠卵巢细胞进行遗传工程改造,使其也稳定地过表达大鼠胰岛素降解酶。与亲本细胞相比,这些细胞表达的酶水平升高了2.7倍,胰岛素降解也增加了2倍。这些细胞在去除胰岛素后也表现出受体酪氨酸磷酸化的更快下降。此外,低浓度的胰岛素在刺激过表达酶的细胞的增殖方面不太有效。最后,在这些细胞的质膜表面上可以检测到一部分过表达的酶以及一部分内源性酶。这些结果支持该酶可能通过降解胰岛素分子在胰岛素信号传导中起作用的假设,(C)1997 Academic Press。
To investigate the role of insulin degrading enzyme (insulysin, EC 3.4.24.56) in insulin signalling, Chinese hamster ovary cells overexpressing the human insulin receptor were genetically engineered to also stably overexpress the rat insulin degrading enzyme. In comparison to the parental cells, these cells expressed 2.7-fold elevated levels of enzyme and insulin degradation was also increased 2-fold. These cells also exhibited a more rapid decrease in receptor tyrosine phosphorylation after removal of insulin. Moreover, low concentrations of insulin were less effective at stimulating proliferation of the cells overexpressing the enzyme, Finally, a fraction of the overexpressed enzyme as well a fraction of the endogenous enzyme could be detected on the plasma membrane surface of these cells. These results support the hypothesis that this enzyme may function in insulin signaling by degrading the insulin molecule, (C) 1997 Academic Press.