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胰岛素受体缺陷细胞作为剖析胰岛素和胰岛素样生长因子复杂相互作用的新工具。

Insulin receptor-deficient cells as a new tool for dissecting complex interplay in insulin and insulin-like growth factors.

作者信息

Lamothe B, Baudry A, Christoffersen C T, De Meyts P, Jami J, Bucchini D, Joshi R L

机构信息

Institut Cochin de Génétique Moléculaire, INSERM U257, Paris, France.

出版信息

FEBS Lett. 1998 Apr 24;426(3):381-5. doi: 10.1016/s0014-5793(98)00377-9.

DOI:10.1016/s0014-5793(98)00377-9
PMID:9600271
Abstract

Cell systems derived from knockout mice for the insulin receptor (IR) or the IGF-1 receptor (IGF-1R) represent unique tools for dissecting complex interplay in the actions of insulin and insulin-like growth factors through their cognate versus non-cognate receptor. In this study, we used a fibroblast cell line derived from IR-deficient mice to investigate metabolic and mitogenic effects of IGF-1 and insulin. IGF-1 was able to stimulate glucose uptake, glucose incorporation into glycogen and thymidine incorporation in such cells. Phosphatidylinositol 3-kinase and mitogen-activated protein kinase, two enzymes of major metabolic-mitogenic signaling pathways, were activated upon stimulating these cells with IGF-1. All these effects were also achieved when IR-deficient cells were stimulated with insulin. Thus, IGF-1R can represent an alternative receptor through which insulin might exert some of its effects.

摘要

源自胰岛素受体(IR)或胰岛素样生长因子-1受体(IGF-1R)基因敲除小鼠的细胞系统,是剖析胰岛素和胰岛素样生长因子通过其同源与非同源受体发挥作用时复杂相互作用的独特工具。在本研究中,我们使用源自IR缺陷小鼠的成纤维细胞系来研究IGF-1和胰岛素的代谢及促有丝分裂作用。IGF-1能够刺激此类细胞摄取葡萄糖、将葡萄糖掺入糖原以及掺入胸苷。在用IGF-1刺激这些细胞时,磷脂酰肌醇3-激酶和丝裂原活化蛋白激酶这两种主要代谢-促有丝分裂信号通路的酶被激活。当用胰岛素刺激IR缺陷细胞时,也能实现所有这些效应。因此,IGF-1R可能是胰岛素发挥某些作用的替代受体。

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