Paradoxical effects of insulin on Tyrosine Aminotransferase : activity and mRNA levels

Tyrosine Aminotransferase (TAT) is inducible by glucocorticoids, estrogens, androgens, growth hormone, cAMP, insulin, and several agents. While glucocorticoids and cAMP increase TAT activity through transcriptional activation of the TAT gene, the mechanism of insulin action has been shown to vary depending on the cell type. Two different mechanisms have been demonstrated in adult rat liver in sulin increases TAT activity through transcriptional act ivation, while in HTC cells insulin increases TAT activity by post-translational stabilization of the TAT enzyme. The mechanism of insulin action has not been defined in H-35 cells. The purpose of this work was to characterize what effects insulin has on TAT mRNA. Enzyme activty assays were done in the presence of DRB, an inhibitor of RNA synthesis, to show that concomitant RNA synthesis is not required for the insulin response. Northern blot analysis usind a cDNA probe revealed that insulin decreases the amount of hybrid-izable TAT mRNA. Finally, transcription in isolated nuclei was measured and results show that insulin decreases TAT transcription. These results are paradoxical. There is an increase in TAT enyzme activity at the same time that there is a decrease in the synthesis of TAT mRNA. A model is presented to account for these results.