TRANSCRIPTIONAL REGULATION OF LIVER PHOSPHOENOLPYRUVATE CARBOXYKINASEBY BIOTIN IN DIABETIC RATS

Rat liver phosphoenolpyruvate carboxykinase (PEPCK) activity was follo wed over a time period of 5 h following administration of biotin to st reptozotocin-induced diabetic rats. In parallel with the decrease in e nzyme activity liver PEPCK mRNA decreased by 85% at 3 h after injectio n of biotin to diabetic rats. There was no significant change in the a ccumulation of kidney PEPCK mRNA. Parallel studies with insulin indica ted that biotin had a regulatory effect similar to that of insulin on liver PEPCK mRNA. The administration of biotin did not change the insu lin status of the diabetic rat indicating that biotin did not act via insulin. The transcriptional activity of the hepatic PEPCK gene, as me asured by nuclear run-on assay, was decreased by 57% within 30 min of biotin administration. The results suggest that biotin regulates hepat ic, but not renal, PEPCK mRNA concentration at the transcriptional lev el in diabetic rats.