Postprandial stimulation of muscle protein synthesis is independent of changes in insulin.
Postprandial stimulation of muscle protein synthesis is independent of changes in insulin.
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餐后肌肉蛋白质合成的刺激与胰岛素的变化无关。
DOI：
10.1152/ajpendo.1997.272.5.e841
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Kimball,SR
中科院分区：
文献类型：
--
作者：
Svanberg,E;Jefferson,LS;Lundholm,K;Kimball,SR
在夜间禁食（18小时）小鼠口服喂养3小时内，骨骼肌蛋白质合成明显受到刺激（约为对照组的180%）。蛋白质合成的刺激是翻译起始速度加快的结果；然而，无论是介质（即激素或营养物质）还是负责喂养效果的机制都没有得到很好的理解。本研究结果显示，与自由喂养小鼠的肌肉相比，一夜饥饿或随后的3小时再喂食期后，以磷酸化形式存在的真核起始因子4E （eIF-4E）的数量（即70%）没有改变。相反，eIF-4E结合蛋白1 （4E-BP1）的磷酸化状态随着营养状态的变化而变化。饥饿增加了未磷酸化形式的4E-BP1的比例，而喂养促进了向高度磷酸化形式的蛋白质的转变。此外，饥饿使4E-BP1的恢复量增加了近三倍，表明eIF-4E增加。4 e - bp1复杂。4E-BP1与eIF-4E增加的相关性在饲喂后3小时内完全逆转。饥饿和再喂养也改变了与eIF-4E共免疫沉淀的eIF-4G的数量。然而，与4E-BP1的结果相反，饥饿减少了eIF-4E免疫沉淀中eIF-4G的恢复量，这表明饥饿导致活性eIF-4F复合物的形成减少。在相同条件下，具有I型或II型糖尿病特征的糖尿病小鼠也观察到饥饿和再喂养时对照小鼠4E-BP1磷酸化的变化以及4E-BP1和eIF-4G与eIF-4E的关联，表明胰岛素单独介导不了所观察到的变化。因此，综合摄食反应是理解翻译起始调控的一个重要研究领域。
Protein synthesis in skeletal muscle is markedly stimulated (approximately 180% of control rate) within 3 h of oral feeding in mice subjected to an overnight fast (18 h). The stimulation of protein synthesis is the result of a faster rate of translation initiation; however, neither the mediators (i.e., hormones or nutrients) nor the mechanisms responsible for the effect of feeding are well understood. Results of the present study revealed that the amount of eukaryotic initiation factor 4E (eIF-4E) present in the phosphorylated form (i.e., 70%) was not changed after overnight starvation or a subsequent 3-h refeeding period compared with muscles from freely fed mice. In contrast, the phosphorylation state of the eIF-4E binding protein 1 (4E-BP1) was changed with nutritional state. Starvation increased the proportion of the unphosphorylated form of 4E-BP1, whereas feeding promoted a shift to the more highly phosphorylated forms of the protein. Moreover, starvation increased the amount of 4E-BP1 recovered by almost threefold, indicative of an increase in the eIF-4E.4E-BP1 complex. The increased association of 4E-BP1 with eIF-4E was completely reversed within 3 h of feeding. Starvation and refeeding also altered the amount of eIF-4G that coimmunoprecipitated with eIF-4E. However, in contrast to the results obtained for 4E-BP1, starvation decreased the amount of eIF-4G recovered in the eIF-4E immunoprecipitate, suggesting that starvation causes a decrease in the formation of the active eIF-4F complex. The alterations in 4E-BP1 phosphorylation and association of 4E-BP1 and eIF-4G with eIF-4E observed in control mice in response to starvation and refeeding were also observed in diabetic mice exhibiting characteristics of type I or type II diabetes subjected to the same conditions, suggesting that insulin alone does not mediate the observed changes. Thus the integrated feeding response represents an important area of investigation for understanding the regulation of translation initiation.