Straus D S, Takemoto C D
J Biol Chem. 1987 Feb 15;262(5):1955-60.
Treatment of cultured H4-II-E rat hepatoma cells with insulin causes a large decrease in cytoplasmic serum albumin mRNA. This effect is observed at low doses of insulin (ED50 = 2 pM), consistent with the effect being mediated by interaction of insulin with high affinity insulin receptors. The reduction in cytoplasmic albumin mRNA is first observed 8-12 h following insulin addition, and albumin mRNA continues to decrease up to 28 h following hormone addition. Northern blot analysis of purified poly(A)+ RNA has indicated that insulin causes a decrease in albumin mRNA relative to total cytoplasmic poly(A)+ RNA. In addition, one other specific mRNA, that encoded by the alpha-tubulin gene, is not decreased following insulin treatment. These results indicate that insulin induces a specific decrease in albumin mRNA. This effect is largely reversed if essential amino acids are added along with the insulin, suggesting that the insulin effect is related to limitation of the cells for essential amino acids. Insulin reduces transcription of the albumin gene 4.7-fold, as measured by nuclear transcription assays. However, this inhibition of albumin gene transcription does not fully account for the 57-fold decrease in albumin mRNA, indicating that insulin also exerts a negative effect on albumin mRNA at a post-transcriptional step.
用胰岛素处理培养的H4-II-E大鼠肝癌细胞会导致细胞质中血清白蛋白mRNA大幅减少。在低剂量胰岛素（ED50 = 2 pM）时即可观察到这种效应，这与该效应是由胰岛素与高亲和力胰岛素受体相互作用介导的一致。在添加胰岛素后8 - 12小时首次观察到细胞质中白蛋白mRNA减少，并且在添加激素后长达28小时白蛋白mRNA持续减少。对纯化的聚腺苷酸加尾（poly(A)+）RNA进行的Northern印迹分析表明，相对于总细胞质聚腺苷酸加尾RNA，胰岛素会导致白蛋白mRNA减少。此外，另一种特定的mRNA，即由α-微管蛋白基因编码的mRNA，在胰岛素处理后并未减少。这些结果表明胰岛素会诱导白蛋白mRNA特异性减少。如果在添加胰岛素的同时添加必需氨基酸，这种效应在很大程度上会被逆转，这表明胰岛素的效应与细胞对必需氨基酸的限制有关。通过细胞核转录分析测定，胰岛素使白蛋白基因的转录减少了4.7倍。然而，白蛋白基因转录的这种抑制并不能完全解释白蛋白mRNA减少57倍的现象，这表明胰岛素在转录后步骤也对白蛋白mRNA产生负面影响。
