Insulin stimulates the degradation of IRS-1 in 3T3-L1 adipocytes.
Insulin stimulates the degradation of IRS-1 in 3T3-L1 adipocytes.
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胰岛素刺激 3T3-L1 脂肪细胞中 IRS-1 的降解。
DOI：
10.1006/bbrc.1993.1143
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发表时间：
1993
影响因子：
3.1
通讯作者：
Garner,CW
中科院分区：
文献类型：
--
作者：
Rice,KM;Turnbow,MA;Garner,CW
胰岛素受体激活后的第一步是 160-185 kDa 胰岛素受体底物 IRS-1 的酪氨酸磷酸化。在 3T3-L1 脂肪细胞中，长期暴露于胰岛素会下调 IRS-1 的表达。 IRS-1 mRNA 的表达基本没有变化。然而，[35S]Met 脉冲追踪标记表明，IRS-1 蛋白的降解速度在胰岛素处理的细胞中比在基底细胞中快约 10 倍。下调发生在放线菌酮或放线菌素 D 存在的情况下，因此不依赖于蛋白质合成。氯喹不会抑制胰岛素诱导的降解，表明蛋白水解位点是溶酶体外的区室。 IRS-1 的胰岛素调节蛋白水解可能导致这些细胞在长期接触胰岛素后出现胰岛素抵抗。
One of the first steps that follows insulin receptor activation is the tyrosine phosphorylation of the 160-185 kDa insulin receptor substrate IRS-1. In 3T3-L1 adipocytes, expression of IRS-1 is down-regulated by chronic exposure to insulin. Expression of IRS-1 mRNA is essentially unchanged. However, [35S]Met pulse-chase labeling demonstrates that the rate of degradation of IRS-1 protein is about 10 times faster in insulin-treated cells than in basal cells. The down-regulation occurs in the presence of cycloheximide or actinomycin D and therefore is not dependent upon protein synthesis. Chloroquine does not inhibit the insulin-induced degradation, suggesting that the site of proteolysis is an extra-lysosomal compartment. The insulin-regulated proteolysis of IRS-1 may contribute to the insulin resistance seen in these cells following chronic exposure to insulin.