Effects of insulin and fructose on transcriptional and post-transcriptional regulation of malic enzyme synthesis in diabetic rat liver.

Insulin action on regulation of hepatic malic enzyme has been investigated in comparison with fructose, using streptozotocin-induced diabetic rats. Insulin-treatment caused a 2.8-fold increase in the transcriptional rate of malic enzyme (EC 1.1.1.40) after 8 h, and a 5-fold increase in the mRNA concentration of the liver. In Northern blot analysis, we demonstrated that after insulin treatment, the nuclear mRNA of malic enzyme tended to increase more rapidly than the total cellular mRNA. Therefore, it is suggested that the nuclear mRNA was primarily increased by insulin. The insulin-dependent increase of malic enzyme mRNA was blocked by cycloheximide, suggesting that synthesis of a peptide is required. On the other hand, by feeding a high-fructose diet to diabetic rats, the malic enzyme mRNA concentration was considerably increased, though with a delayed peaking in comparison with the insulin-treated animals, whereas the transcriptional rate was not significantly increased. Dietary fructose may stabilize the transcripts. Fructose increased the enzyme level far less than the mRNA level. These results suggest that insulin is required in both the translational and transcriptional regulation of malic enzyme.