Insulin negatively regulates albumin mRNA at the transcriptional and post-transcriptional level in rat hepatoma cells.

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.