Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic β cells
Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic β cells
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DOI：
10.1016/s1097-2765(01)00203-9
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发表时间：
2001-03-01
期刊：
影响因子：
16
通讯作者：
Berggren, PO
中科院分区：
文献类型：
--
作者：
Leibiger, B;Leibiger, IB;Berggren, PO
胰岛素信号传导是由一个复杂的网络，发散和收敛的途径，与替代蛋白质和亚型在几乎每一个步骤的过程。我们在这里表明，胰岛素激活自己的基因和8细胞葡萄糖激酶基因（PGK）的转录通过不同的机制。尽管胰岛素基因转录通过经由胰岛素受体A型（Ex 11-）、PI 3 K Ia类和p70 s6 k的信号传导来促进，但胰岛素通过经由胰岛素受体B型（Ex 11+）、PI 3 K II类活性和PK B（c-Akt）的信号传导来刺激PGK基因。我们的数据提供了通过胰岛素受体的两种亚型的胰岛素作用的选择性的证据，分子基础是通过不同的PI 3 K和蛋白激酶的优先信号传导。
Insulin signaling is mediated by a complex network of diverging and converging pathways, with alternative proteins and isoforms at almost every step in the process. We show here that insulin activates the transcription of its own gene and that of the 8 cell glucokinase gene (PGK) by different mechanisms. Whereas insulin gene transcription is promoted by signaling through insulin receptor A type (Ex11-), PI3K class la, and p70s6k, insulin stimulates the PGK gene by signaling via insulin receptor B type (Ex11+), PI3K class Ii-like activity, and PKB (c-Akt). Our data provide evidence for selectivity in insulin action via the two isoforms of the insulin receptor, the molecular basis being preferential signaling through different PI3K and protein kinases.