Altered function of insulin receptor substrate-1-deficient mouse islets and cultured β-cell lines
Altered function of insulin receptor substrate-1-deficient mouse islets and cultured β-cell lines
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DOI：
10.1172/jci8339
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发表时间：
1999-12-01
影响因子：
15.9
通讯作者：
Kahn, CR
中科院分区：
文献类型：
--
作者：
Kulkarni, RN;Winnay, JN;Kahn, CR
胰岛素受体底物-1(IRS-1)在调节胰岛素和生长因子在体内大多数组织中的作用中起着关键作用，但它在产生胰岛素的胰岛细胞中的作用尚不清楚。从IRS-I基因敲除小鼠和SV40转化的IRS-L缺陷的β细胞系中新分离的胰岛对葡萄糖和精氨酸的反应显示出显著的胰岛素分泌缺陷。此外，胰岛素样生长因子-L缺失的胰岛和胰岛β细胞系中胰岛素的表达减少了约2倍，这种缺陷可以通过转导胰岛素样生长因子-1的细胞部分修复。这些数据为IRS-1在胰岛功能中的重要作用提供了证据，并提供了胰岛素信号和胰岛素分泌途径之间的新的功能联系。
Insulin receptor substrate-1 (IRS-1) is pivotal in mediating the actions of insulin and growth factors in most tissues of the body, but its role in insulin-producing beta islet cells is unclear. Freshly isolated islets from IRS-I knockout mice and SV40-transformed IRS-l-deficient beta-cell lines exhibit marked insulin secretory defects in response to glucose and arginine. Furthermore, insulin expression is reduced by about 2-fold in the IRS-l-null islets and beta-cell lines, and this defect can be partially restored by transfecting the cells with IRS-1. These data provide evidence for an important role of IRS-1 in islet function and provide a novel functional link between the insulin signaling and insulin secretion pathways.