Differential effects of okadaic acid on insulin-stimulated glucose and amino acid uptake and phosphatidylinositol 3-kinase activity.
Differential effects of okadaic acid on insulin-stimulated glucose and amino acid uptake and phosphatidylinositol 3-kinase activity.
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冈田酸对胰岛素刺激的葡萄糖和氨基酸摄取以及磷脂酰肌醇 3-激酶活性的不同影响。
DOI：
10.1016/s0021-9258(18)82462-0
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Y. Le Marchand
中科院分区：
文献类型：
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作者：
D. Jullien;J. Tanti;S. Heydrick;N. Gautier;T. Grémeaux;E. van Obberghen;Y. Le Marchand
冈田酸，丝氨酸/苏氨酸磷酸酶抑制剂，的影响进行了分析，在两个胰岛素响应系统，分离的小鼠比目鱼肌和3 T3-L1脂肪细胞。而冈田酸单独是一个有效的刺激剂葡萄糖转运在这两个系统中，它阻止了胰岛素的运输刺激。为了深入了解这种抑制作用，磷脂酰肌醇3-激酶（PI 3-激酶），迄今为止确定的最早的postreceptor步骤之一的激活进行了研究。在3 T3-L1脂肪细胞和肌肉中，胰岛素增加了磷酸酪氨酸抗体免疫沉淀物中PI 3-激酶的活性。冈田酸单独没有影响，但强烈抑制这种激素作用。冈田酸处理不干扰胰岛素诱导的受体自磷酸化或其酪氨酸激酶活性对人工底物。相反，在磷酸酶抑制剂的存在下，我们没有观察到酪氨酸磷酸化的胰岛素受体细胞底物p185（IRS-1）或免疫沉淀的PI 3-激酶的抗体磷酸酪氨酸。这些结果表明冈田酸通过抑制IRS-1磷酸化及其与PI 3-激酶和/或其他信号分子的结合来干扰胰岛素对葡萄糖转运的刺激。然而，冈田酸并不阻断胰岛素刺激肌肉摄取氨基异丁酸。这将表明IRS-1磷酸化和PI 3-激酶激活不是胰岛素所有作用所必需的，并且葡萄糖转运蛋白易位中涉及的丝氨酸/苏氨酸磷酸化事件并不控制肌肉中的氨基酸转运。
The effect of okadaic acid, a serine/threonine phosphatase inhibitor, was analyzed in two insulin-responsive systems, the isolated mouse soleus muscle and 3T3-L1 adipocytes. While okadaic acid alone was a potent stimulator of glucose transport in both systems, it prevented transport stimulation by insulin. To gain insight into this inhibitory action, the activation of phosphatidylinositol 3-kinase (PI3-kinase), one of the earliest postreceptor steps identified so far, was studied. In 3T3-L1 adipocytes and muscle, insulin increased PI3-kinase activity in immunoprecipitates obtained with antibodies to phosphotyrosine. Okadaic acid alone had no effect but strongly inhibited this hormonal action. Okadaic acid treatment did not interfere with insulin-induced receptor autophosphorylation or with its tyrosine kinase activity toward artificial substrates. In contrast, in the presence of the phosphatase inhibitor, we did not observe tyrosine phosphorylation of the insulin receptor cellular substrate p185 (IRS-1) or immunoprecipitation of PI3-kinase by antibodies to phosphotyrosine. These results suggest that okadaic acid interferes with insulin's stimulation of glucose transport by inhibiting IRS-1 phosphorylation and its association with PI3-kinase and/or other signaling molecules. However, okadaic acid did not block the insulin stimulation of aminoisobutyric acid uptake in muscle. This would indicate that IRS-1 phosphorylation and PI3-kinase activation are not required for all the effects of insulin and that the serine/threonine phosphorylation events implicated in the translocation of glucose transporters are not controlling amino acid transport in muscle.