Differential regulation of MAP kinase by contraction and insulin in skeletal muscle: metabolic implications
Differential regulation of MAP kinase by contraction and insulin in skeletal muscle: metabolic implications
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DOI：
10.1152/ajpendo.1999.277.4.e724
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发表时间：
1999-10-01
影响因子：
5.1
通讯作者：
Richter, EA
中科院分区：
文献类型：
--
作者：
Wojtaszewski, JFP;Lynge, J;Richter, EA
骨骼肌收缩和胰岛素对MAP激酶的差异调节：代谢意义。我们研究了在灌流的大鼠骨骼肌中，肌肉收缩和胰岛素对细胞外信号调节的Era激酶（ERK 1和ERK 2）的激活。两种刺激都通过上游激酶MAP/ERK激酶（MEK）依赖性机制激活ERK 1和ERK 2，因为MEK抑制剂PD-98059抑制ERK磷酸化。磷脂酰肌醇（PI）3-激酶抑制剂LY-294002和渥曼青霉素的存在下完全根除ERK 1和ERK 2的磷酸化响应胰岛素，但不收缩。胰岛素和肌肉收缩激活肌肉葡萄糖转运，糖原合成酶，氨基酸转运独立的ERK信号，而PI 3-激酶抑制剂废除胰岛素的刺激作用，但不是这些收缩对这三个细胞过程。我们的结论是：1）胰岛素和收缩激活骨骼肌中的ERK信号; 2）ERK信号不是骨骼肌中收缩和胰岛素激活葡萄糖和氨基酸转运或糖原合成酶活性所必需的; 3）胰岛素诱导的ERK上游激活剂MEK的激活依赖于PI 3-激酶，而收缩利用不同的机制。
Differential regulation of MAP kinase by contraction and insulin in skeletal muscle: metabolic implications. We have investigated the activation of the extracellular signal-regulated Era kinases (ERK1 and ERK2) by muscle contraction and insulin in perfused rat skeletal muscle. Both stimuli activated ERK1 and ERK2 by an upstream kinase MAP/ERK kinase (MEK)dependent mechanism, as the MEK inhibitor PD-98059 inhibited ERK phosphorylation. The presence of the phosphatidylinositol (PI) 3-kinase inhibitors LY-294002 and wortmannin totally eradicated ERK1 and ERK2 phosphorylation in response to insulin but not contraction. Insulin and muscle contraction activated muscle glucose transport, glycogen synthase, and amino acid transport independently of ERK signaling, whereas the PI 3-kinase inhibitors abolished the stimulatory effects of insulin but not those of contraction on these three cellular processes. We conclude that 1) insulin and contraction activate ERK signaling in skeletal muscle; 2) ERK signaling is not necessary for activation of glucose and amino acid transport or glycogen synthase activity by contraction and insulin in skeletal muscle; and 3) insulin-induced activation of MEK, the upstream activator of ERK, is dependent on PI 3-kinase, whereas contraction utilizes a different mechanism.