Fructose-1,6-bisphosphate as a metabolic substrate in hog ileum smooth muscle during hypoxia.
Exogenously applied fructose-1,6-bisphosphate has been reported to be effective in preventing some damage to the small intestine during ischemia. To determine whether exogenously applied fructose-1,6-bisphosphate protects ileum smooth muscle from damage from hypoxia and from reoxygenation, we examined the effect of fructose-1,6-bisphosphate on the ability of hog ileum smooth muscle to maintain isometric force during hypoxia and to generate isometric force after reoxygenation in the presence of 5 mM glucose. After 180 min of hypoxia, tissues incubated with 20 mM fructose-1,6-bisphosphate maintained significantly greater levels of isometric force than tissues incubated in the absence of exogenous substrate (23% of pre-hypoxia force compared to 16%). During the first contraction following reoxygenation there was a significantly greater force generation in tissues incubated with 20 mM fructose-1,6-bisphosphate during the hypoxia period compared to tissues with no exogenous substrate included during the hypoxia period (29% of pre-hypoxia force compared to 19%). However, glucose always was a better metabolic substrate compared to fructose-1,6-bisphosphate under all experimental conditions. The presence of fructose-1,6-bisphosphate during hypoxia likely improved tissue function by fructose-1,6-bisphosphate entering the cells and acting as a glycolytic intermediate, since during a 120 min period of hypoxia, unmounted ileum smooth muscle metabolized 1,6-13C-fructose-1,6-bisphosphate to 3-13C-lactate. This conversion of 1,6-13C-fructose-1,6-bisphosphate to 3-13C-lactate was inhibited by the addition of 1 mM iodoacetic acid, a glycolytic inhibitor. We conclude that exogenously provided fructose-1,6-bisphosphate does provide modest protection of ileum smooth muscle from hypoxic damage by functioning as a glycolytic intermediate and improving the cellular energy state.
Juergens
T M
TM
Department of Physiology, University of Missouri, Columbia 65212, USA.
Hardin
C D
CD
D000818:Animals; D002247:Carbon Isotopes; D005635:Fructosediphosphates / Q000378:metabolism* / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D000860:Hypoxia; D007082:Ileum; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D002247:Carbon Isotopes; D005635:Fructosediphosphates; D005947:Glucose; C029063:fructose-1,6-diphosphate