Alcohol impairs insulin and IGF-I stimulation of S6K1 but not 4E-BP1 in skeletal muscle
Alcohol impairs insulin and IGF-I stimulation of S6K1 but not 4E-BP1 in skeletal muscle
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DOI：
10.1152/ajpendo.00181.2002
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发表时间：
2002-11-01
影响因子：
5.1
通讯作者：
Lang, CH
中科院分区：
文献类型：
--
作者：
Kumar, V;Frost, RA;Lang, CH
本研究确定了大鼠急性酒精(乙醇；乙醇)中毒是否损害了骨骼肌中胰岛素和IGF-I信号通路的组成部分。给大鼠注射乙醇，2.5h后注射胰岛素、IGF-I或生理盐水，摘除腓肠肌。在基础或激素刺激条件下，乙醇不改变胰岛素受体、IGF-I受体、胰岛素受体底物(IRS)-1或蛋白激酶B(PKB)/Akt的总量或酪氨酸磷酸化。相反，胰岛素或IGF-I对S6K-1上T389和T421/S424的磷酸化能力被乙醇显著降低，这些变化与核糖体蛋白S6的磷酸化减少有关。在基础条件下，乙醇改变了真核细胞起始因子(EIF)4E的分布，其证据是活性eIF4E的数量减少。EIF4G复合体，增加了非活动eIF4E的数量。4E结合蛋白(BP)1复合体，降低4E-BP1的磷酸化。相反，乙醇不损害任何一种激素逆转eIF4E分布或4E-BP1磷酸化的能力。用糖皮质激素受体拮抗剂预处理既不能减弱基础乙醇引起的eIF4E分布的改变，也不能减弱IGF-I刺激S6K1和S6磷酸化的能力受损。因此，急性酒精中毒在基础和合成激素刺激的条件下，以糖皮质激素非依赖的方式改变了骨骼肌中翻译控制的特定方面。
The present study determined whether acute alcohol (ethanol; EtOH) intoxication in rats impaired components of the insulin- and IGF-I-signaling pathway in skeletal muscle. Rats were administered EtOH, and 2.5 h thereafter either insulin, IGF-I, or saline was injected and the gastrocnemius removed. EtOH did not alter the total amount or tyrosine phosphorylation of the insulin receptor, IGF-I receptor, insulin receptor substrate (IRS)-1, or protein kinase B (PKB)/Akt under basal or hormone-stimulated conditions. In contrast, the ability of insulin or IGF-I to phosphorylate T389 and T421/S424 on S6K-1 was markedly diminished by EtOH, and these changes were associated with a reduction in the phosphorylation of the ribosomal protein S6. Under basal conditions, EtOH altered the distribution of eukaryotic initiation factor (eIF) 4E, as evidenced by a decreased amount of active eIF4E . eIF4G complex, an increased amount of inactive eIF4E . 4E-binding protein (BP) 1 complex, and decreased 4E-BP1 phosphorylation. In contrast, EtOH did not impair the ability of either hormone to reverse the changes in eIF4E distribution or 4E-BP1 phosphorylation. Pretreatment with a glucocorticoid receptor antagonist was unable to attenuate either the basal EtOH-induced changes in eIF4E distribution or the impaired ability of IGF-I to stimulate S6K1 and S6 phosphorylation. Hence, acute alcohol intoxication alters selected aspects of translational control under both basal and anabolic hormone-stimulated conditions in skeletal muscle in a glucocorticoid-independent manner.