Glucose: a more powerful modulator of fructose 2,6-bisphosphate levels than insulin in human hepatocytes.
This study provides the first experimental evidence of the short-term control of fructose 2,6-bisphosphate (Fru(2,6)P2) 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 beta-adrenergic agonist) and lactate exerted a similar action decreasing Fru(2,6)P2 concentration. (2) In glucagon pre-treated, glycogen- and Fru(2,6)P2-depleted cells (a situation that mimics the fasted state), Fru(2,6)P2 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)P2 in human hepatocytes. The hormone--which failed to enhance Fru(2,6)P2 in glucose-starved cells--did not further increase Fru(2,6)P2 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)P2 content that could not be prevented by insulin. (5) Data indicate that in human hepatocytes glucose is a more powerful modulator of Fru(2,6)P2 than insulin, and that variations in blood lactate concentration may also play a role in the control of hepatic Fru(2,6)P2 levels during the fasted-to-fed transition in humans.
López
M P
MP
Experimental Hepatology Unit, Hospital La Fe, Valencia, Spain.
Gómez-Lechón
M J
MJ
Castell
J V
JV
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005635:Fructosediphosphates / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000502:physiology*; D006019:Glycolysis; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000502:physiology*; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D013565:Sympatholytics / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology
D005635:Fructosediphosphates; D007328:Insulin; D007773:Lactates; D008112:Liver Glycogen; D013565:Sympatholytics; D013566:Sympathomimetics; C027652:fructose 2,6-diphosphate; D005934:Glucagon; D005947:Glucose