Effects of nutrients and insulin on transcriptional and post-transcriptional regulation of glucose-6-phosphate dehydrogenase synthesis in rat liver.

The transcriptional and post-transcriptional regulation of glucose-6-phosphate dehydrogenase induction of rat liver was investigated using a cDNA cloned in our laboratory. By feeding a carbohydrate/protein diet to fasted rats, the mRNA concentration and enzyme induction of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) reached maximal levels about 10-fold those in the fasted rats at 16 h and 72 h, respectively, whereas the transcriptional rate was increased about 3-fold in 6 h. In the protein fed (without carbohydrate) group, both the mRNA concentration and enzyme induction were increased to about 60% of the levels in the carbohydrate/protein fed group and in the group fed on a carbohydrate diet (without protein) to 30-40%. Further, dietary fat significantly reduced the transcriptional rate, mRNA concentration and enzyme induction to less than half, suggesting that dietary fat primarily reduced transcription. Thus, dietary nutrients appear to be involved in the steps preceding the translation. On the other hand, in diabetic rats, the transcriptional rate was significantly decreased as compared to the normal level and restored by insulin-treatment in 4 h. The mRNA concentration was very low in diabetic rats, and was restored to the normal level by insulin treatment in 8 h, and was half restored by fructose feeding. However, the enzyme induction of glucose-6-phosphate dehydrogenase was scarcely restored by fructose, unless accompanied by insulin treatment. Thus, it is suggested that insulin is involved in translation as well as in transcription. Further, the insulin-dependent increase of glucose-6-phosphate dehydrogenase mRNA was blocked by cycloheximide, suggesting that synthesis of a peptide is required.