REGULATION OF HEPATIC 6-PHOSPHOFRUCTO-2-KINASE FRUCTOSE 2,6-BISPHOSPHATASE GENE-EXPRESSION BY GLUCAGON

The control of hepatic 6-phosphofructo-2-kinase/fructose 2,6-bisphosph atase gene expression by glucagon was studied. Intraperitoneal adminis tration of glucagon rapidly decreased the fructose 2,6-bisphosphate co ntent by phosphorylation of 6-phosphofructo-2-kinase/fructose 2,6-bisp hosphatase and diminution of its V(max). Immunologic studies using a s pecific liver antibody showed that the amount of enzyme rapidly decrea sed. Northern blot analysis showed that the isozyme expressed is the a dult liver form. The 6-phosphofructo-2-kinase/fructose 2,6-bisphosphat ase mRNA content decreased, whereas that of phosphoenolpyruvate carbox ykinase increased, and that of albumin did not change. Run-on transcri ption assays with isolated nuclei showed inhibition in the relative tr anscription rate of the 6-phosphofructo-2-kinase/fructose 2,6-bisphosp hatase gene and a stimulation of phosphoenolpyruvate carboxykinase gen e. The regulation of mRNA stability of 6-phosphofructo-2-kinase/fructo se 2,6-bisphosphatase by glucagon was also studied. The half-life of m RNA decreased in the presence of glucagon, suggesting that proteins mo dulated by a glucagon-dependent process are regulating its stability. The time course of mRNA levels correlated with the transcription inhib ition of gene and destabilization of mRNA, indicating that glucagon mo dulates 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase gene expr ession at both transcriptional and posttranscriptional levels.