Induction of hepatic ATP-citrate lyase by insulin in diabetic rat--effects of insulin on the contents of enzyme and its mRNA in cytosol, and the transcriptional activity in nuclei.

Abstract

The effects of insulin on ATP-citrate lyase, its mRNA in cytosol, and the transcriptional activity in nuclei of diabetic rat liver were studied. Experimental diabetes was induced by an intraperitoneal injection of streptozotocin, and livers were removed from rats at 0, 1, 3, 6, 16, and 72 hours after the administration of insulin. ATP-citrate lyase began to increase at 16 hours, and continuously increased until 72 hours. The amount of mRNA encoding ATP-citrate lyase increased abruptly at 16 hours, then decreased to near basal level in 72 hours. No change in the transcription rate was observed until 3 hours after insulin administration. However, the activity increased 4-fold at 6 hours and 7-fold at 16 hours, 16-fold at 6 hours and 28-fold at 16 hours when pGACL1 and pGACL2 were used as probes, respectively, preceding the increase in the amounts of mRNA and the enzyme. It is suggested that the increase in the amount of ATP-citrate lyase by insulin is primarily due to the increase in the transcriptional activity of the gene in nuclei, which results in the subsequent increase in the amount of mRNA for the biosynthesis of ATP-citrate lyase in cytosol.