Nutritional state regulates insulin receptor and IRS-1 phosphorylation and expression in chicken
Nutritional state regulates insulin receptor and IRS-1 phosphorylation and expression in chicken
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DOI：
10.1152/ajpendo.1998.274.2.e309
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发表时间：
1998-02-01
影响因子：
5.1
通讯作者：
Taouis, M
中科院分区：
文献类型：
--
作者：
Dupont, J;Derouet, M;Taouis, M
胰岛素结合后，胰岛素受体（IR）磷酸化特定基序上的胰岛素受体底物1（IRS-1），从而启动胰岛素作用。IR和IRS-1之间的相互作用和它们的表达进行了研究，在体内的两个靶组织（肌肉和肝脏）在鸡，一个物种，是胰岛素抵抗。为了诱导血浆胰岛素水平的极端变化，将鸡置于三种不同的营养状态下（自由采食、禁食48小时和禁食48小时后再进食30分钟）。禁食组肝细胞膜IR数显著高于饲喂组。逆转录-聚合酶链反应测定IR数量的上调与IR mRNA表达的增强相伴随。在腿肌中，IR mRNA。并不因营养状况而改变。使用针对人IR、抗磷酸酪氨酸或小鼠IRS-1的特异性抗体，我们证明了IR和IRS-1在体内肝脏和肌肉中相关。肝脏IR和IRS-1的酪氨酸磷酸化显着降低，延长禁食和恢复30分钟的再喂养。在肌肉中未观察到这些变化。禁食增加肝脏IRS-1 mRNA的表达，但在肌肉中没有。这些结果首次证明鸡肝脏和肌肉表达IRS-1。因此，鸡的胰岛素抵抗不是由于IRS-1的缺乏。观察到的差异调节IR和IRS-1信使和磷酸化之间的肝脏和肌肉的营养状态的改变仍有待解释。
After insulin binding, insulin receptors (IR) phosphorylate the insulin receptor substrate 1 (IRS-1) on specific motifs and thereby initiate insulin action. The interaction between IR and IRS-1 and their expression were studied in vivo in two target tissues (muscle and liver) in chickens, a species that is insulin resistant. To induce extreme changes in plasma insulin levels, chickens were subjected to three different nutritional states (ad libitum fed, fasted for 48 h, and refed for 30 min after 48-h fast). Liver membrane IR number was significantly increased in fasted compared with fed chickens. This upregulation of IR number was concomitant with the an enhanced expression of IR mRNA as determined by reverse transcription-polymerase chain reaction. In leg muscle, IR mRNA. was not altered by the nutritional state. Using specific antibodies directed toward human IR, anti-phosphotyrosines, or mouse IRS-1, we demonstrated that IR and IRS-1 are associated in vivo in liver and muscles. Tyrosine phosphorylation of liver IR and IRS-1 were significantly decreased by prolonged fasting and restored by 30-min refeeding. These alterations were not observed in muscle. Fasting increased IRS-1 mRNA expression in liver but not in muscle. These results are the first evidence showing that chicken liver and muscle express IRS-1. Therefore, the chicken insulin resistance is not accounted for by the lack of IRS-1. The differences observed for the regulation of IR and IRS-1 messengers and phosphorylation between liver and muscle in response to alterations of the nutritional state remain to be explained.