title: Fructose-2,6-bisphosphate, a potent stimulator of phosphofructokinase, is increased by high exogenous glucose perfusion.
abstract: BACKGROUND
  We have previously demonstrated that perfusion of isolated hearts with high concentrations of glucose results in increased glycolysis during ischemia, diminished ischemic injury, and improved functional recovery with reperfusion.
  
  
  OBJECTIVE
  To evaluate a possible mechanism by which glucose conferred this protection. We examined the hypothesis that increased exogenous glucose concentrations results in increased concentrations of fructose-2,6-bisphosphate, a potent activator of phosphofructokinase-1, and thus increases glycolysis.
  
  
  METHODS
  Perfused rabbit hearts were subjected to 60 min of low-flow ischemia. Control hearts were perfused with buffer containing 0.4 mmol/l palmitate, 5 mmol/l glucose, and 70 mU/l insulin, and treated hearts were perfused with buffer containing 0.4 mmol/l palmitate, 15 mmol/l glucose and 210 mU/l insulin.
  
  
  RESULTS
  Ischemic contracture was attenuated by perfusion of high concentrations of glucose (high glucose) (P < 0.05 compared with control). Glucose uptake and lactate production were greater in hearts perfused with high glucose, as was the ATP concentration at the end of ischemia (P < 0.05 compared with controls). Exogenous glucose uptake and lactate production correlated well with fructose-2,6-bisphosphate content (P = 0.007).
  
  
  CONCLUSIONS
  Enhancement of glycolysis in hearts perfused with high glucose may be the result of stimulation of phosphofructokinase-1 by fructose-2,6-bisphosphate. Accordingly, this may serve as an important mechanism by which cardioprotection may be achieved.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Salaris
authors.forename: R
authors.initials: R
authors.lastname: Ramasamy
authors.forename: S R
authors.initials: SR
authors.lastname: Bergmann
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics; D019344:Lactic Acid / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D010732:Phosphofructokinase-1 / Q000378:metabolism; D025481:Phosphofructokinase-2; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011817:Rabbits
chemical_list: D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D025481:Phosphofructokinase-2; D010732:Phosphofructokinase-1; D010744:Phosphoric Monoester Hydrolases; D005947:Glucose