Glucose: a more powerful modulator of fructose 2,6-bisphosphate levels than insulin in human hepatocytes.

Abstract This study provides the first experimental evidence of the short-term control of fructose 2,6-bisphosphate (Fru(2,6) P 2 ) levels in adult human hepatocytes. (1) In hepatocytes whose metabolic status resembles the fed state (glycogen-rich), exposure to glucagon (10 −8 M) caused a drastic decrease in the levels of this effector and a significant fall in lactate production rate. Adrenaline, isoprenaline (a β-adrenergic agonist) and lactate exerted a similar action decreasing Fru(2,6) P 2 concentration. (2) In glucagon pre-treated, glycogen- and Fru(2,6) P 2 -depleted cells (a situation that mimics the fasted state), Fru(2,6) P 2 re-synthesis was strictly dependent on glucose availability. (3) Insulin did not seem to exert a direct action on the control of Fru(2,6) P 2 in human hepatocytes. The hormone - which failed to enhance Fru(2,6) P 2 in glucose-starved cells - did not further increase Fru(2,6) P 2 content nor its time-course evolution as compared to hepatocytes incubated with glucose alone. (4) Lactate caused a significant delay in the glucose-induced increase in Fru(2,6) P 2 content that vould not be prevented by insulin. (5) Data indicate that in human hepatocytes glucose is a more powerful modulator of Fru(2,6) P 2 than insulin, and that variations in blood lactate concentration may also play a role in the control of hepatic Fru(2,6) P 2 levels during the fasted-to-fed transition in humans.