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: S C Salaris, R Ramasamy, S R Bergmann
• Journal: Coronary artery disease (Coron Artery Dis) Vol. 11 Issue 3 Pg. 279-86 (May 2000) ISSN: 0954-6928 [Print] England
• PMID: 10832563 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Lactic Acid
• Adenosine Triphosphate
• Glycogen
• Phosphofructokinase-2
• Phosphofructokinase-1
• Phosphoric Monoester Hydrolases
• Glucose

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Glucose (metabolism, pharmacology)
• Glycogen (metabolism)
• Glycolysis (drug effects, physiology)
• Hemodynamics
• Lactic Acid (metabolism)
• Myocardial Ischemia (metabolism, physiopathology)
• Phosphofructokinase-1 (metabolism)
• Phosphofructokinase-2
• Phosphoric Monoester Hydrolases (metabolism)
• Rabbits