Insulin inhibits glucocorticoid-induced stimulation of liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene transcription.

6-Phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase (FBPase-2) catalyzes the synthesis and degradation of fructose 2,6-bisphosphate, a potent stimulator of glycolysis. Transcription of the mRNA encoding rat liver PFK-2/FBPase-2 is stimulated by insulin and by glucocorticoids in rat hepatoma cells. We show here that insulin can also prevent and reverse this glucocorticoid effect. The inhibitory effect of insulin is independent of extracellular glucose and does not require ongoing protein synthesis. We conclude that insulin exerts opposite effects on PFK-2/FBPase-2 gene transcription depending on the hormonal context.