Difference in glucose sensitivity of liver glycolysis and glycogen synthesis. Relationship between lactate production and fructose 2,6-bisphosphate concentration.
Incubation of isolated rat hepatocytes from fasted rats with 0-6 mM-glucose caused an increase in [fructose 2,6-bisphosphate] (0.2 to about 5 nmol/g) without net lactate production. A release of 3H2O from [3-3H]glucose was, however, detectable, indicating that phosphofructokinase was active and that cycling occurred between fructose 6-phosphate and fructose 1,6-bisphosphate. A relationship between [fructose 2,6-bisphosphate] and lactate production was observed when hepatocytes were incubated with [glucose] greater than 6 mM. Incubation with glucose caused a dose-dependent increase in [hexose 6-phosphates]. The maximal capacity of liver cytosolic proteins to bind fructose 2,6-bisphosphate was 15 nmol/g, with affinity constants of 5 X 10(6) and 0.5 X 10(6) M-1. One can calculate that, at 5 microM, more than 90% of fructose 2,6-bisphosphate is bound to cytosolic proteins. In livers of non-anaesthetized fasted mice, the activation of glycogen synthase was more sensitive to glucose injection than was the increase in [fructose 2,6-bisphosphate], whereas the opposite situation was observed in livers of fed mice. Glucose injection caused no change in the activity of liver phosphofructokinase-2 and decreased the [hexose 6-phosphates] in livers of fed mice.
D000818:Animals; D003600:Cytosol / Q000378:metabolism; D005635:Fructosediphosphates / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects*; D006600:Hexosephosphates / Q000378:metabolism; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D051379:Mice; D010732:Phosphofructokinase-1 / Q000378:metabolism; D051381:Rats
D005635:Fructosediphosphates; D006600:Hexosephosphates; D007773:Lactates; D008112:Liver Glycogen; D019344:Lactic Acid; C027652:fructose 2,6-diphosphate; D010732:Phosphofructokinase-1; D005947:Glucose