Improved brain metabolism with fructose 1-6 diphosphate during insulin-induced hypoglycemic coma

Farias, Lorenzo A.; Sun, Jia-Xiang; Markov, Angel K.

doi:10.1097/00000441-198905000-00005

Cited by 19 publications

(9 citation statements)

References 25 publications

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“…25 Furthermore, FDP restored electroencephalographic (EEG) activity during hypoglycemic coma in rabbits and improved recovery of neurophysiologic functions after restitution of normoglycemia with glucose. 26 These data indicate that FDP might afford protection to the brain during ischemia-hypoxia. With these concepts in mind, the present study was designed to investigate whether the intravenous administration of FDP to rabbits subjected to ischemic-hypoxic brain insult attenuates brain injury and increases survival.…”

mentioning

confidence: 85%

“…This possibility is consistent with our previous report that FDP administration induced a return of EEG activity during hypoglycemic coma and that EEG activity recovered a pattern similar to that before the coma following resolution of the hypoglycemia with glucose. 26 It has also been shown that systemic administration of FDP prolongs the time required for the EEG to become isoelectric during anoxemia and improves the reoxidation of cytochrome a 3 during reoxygenation of cat brain. 24 Histologic evaluation demonstrated that the brains of controls that survived >48 hours exhibited extensive necrosis of the neocortex as well as focal necrosis in the hippocampi and cerebellum, whereas FDPtreated rabbits subjected to the same or more severe hypoxic-ischemic insult had less histologically detectable injury, consisting of small confluent foci of necrosis limited to the neocortex.…”

Section: Figure 3 Electroencephalograms (Eegs) Before (Control) and mentioning

confidence: 99%

“…- 26 FDP prolonged survival during severe hypoxemia and improved short-term neurologic recovery of rabbits successfully resuscitated from cardiac arrest. 25 Furthermore, FDP restored electroencephalographic (EEG) activity during hypoglycemic coma in rabbits and improved recovery of neurophysiologic functions after restitution of normoglycemia with glucose.…”

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confidence: 95%

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Prevention of ischemic-hypoxic brain injury and death in rabbits with fructose-1,6-diphosphate.

Farias

Smith

Markov

1990

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Fructose-l,6-diphosphate has been shown to improve neurologic recovery following resuscitation from cardiac arrest and to restore brain electrical activity during hypoglycemic coma in rabbits. In view of these findings, we determined whether fructose-1,6-diphosphate protects the brain during ischemia-hypoxia. We subjected 16 rabbits to hypotension, hypoxemia, and bilateral common carotid artery occlusion. Five minutes after the onset of isoelectric electroencephalograms, seven randomly selected rabbits received 10% fructose-l,6-diphosphate (350 mg/kg bolus followed by 10 mg/kg/min infusion for 90 minutes) and the remaining nine rabbits (controls) received an equal volume of 1.5% NaCl (3.5 ml/kg bolus followed by 0.1 ml/kg/min infusion for 90 minutes). After isoelectricity lasting 7.86±0.8 minutes (mean±SEM) in the treated group and 6.44 ±0.38 minutes in the control group, the rabbits were reinfused with autologous shed blood and reoxygenated and the carotid artery occluders were removed. Treated rabbits recovered electrical activity more rapidly than the controls (p<0.005), and all seven treated rabbits survived. Only two controls (22%) survived (p<0.001), and they were severely disabled. Histology showed extensive cortical necrosis and focal necrosis in the hippocampi and cerebellum of brains from the two surviving controls. Brains from two treated rabbits exhibited minimal neuronal loss limited to the neocortex, and the brains from the remaining five treated rabbits were normal. This study suggests that fructose-1,6 -diphosphate protects the brain from ischemic-hypoxic insults.

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confidence: 85%

Section: Figure 3 Electroencephalograms (Eegs) Before (Control) and mentioning

confidence: 99%

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Prevention of ischemic-hypoxic brain injury and death in rabbits with fructose-1,6-diphosphate.

Farias

Smith

Markov

1990

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“…Although it is a phosphorylated sugar, FBP crosses the blood-brain barrier and enters neurons. 7 Possible intracellular actions of FBP during hypoxia or ischemia include 1) stimulation of carbohydrate metabolism through activation of phosphofructokinase 8 -9 ; 2) increased carbon flux through the pentose phosphate pathway (G. Gregory, J. Kelleher, T.Y. Chan, and P. Chan, unpublished observations); 3) direct glycolytic metabolism of FBP, with resulting ATP production 7 ; and 4) prevention of oxygen-derived free radical injury.…”

Section: Fructose-16-bisphosphate Stabilizes Brain Intracellular Calmentioning

confidence: 99%

Fructose-1,6-bisphosphate stabilizes brain intracellular calcium during hypoxia in rats.

Bickler

Kelleher

1992

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“…Despite the clear effect of FDP on seizure activity, the question remains whether FDP can get into the brain. In earlier experiments it was shown that administration of FDP to rabbits during hypoglycemic coma (5) or ischemia-hypoxia and reperfusion (6) improved outcomes. Experiments have also shown alterations in pyruvate levels in the brain of pigs after intravenous administration of FDP (7).…”

Section: Introductionmentioning

confidence: 98%

Pharmacokinetics of fructose-1,6-diphosphate after intraperitoneal and oral administration to adult rats

Stringer

2008

Pharmacological Research

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Exogenously administered fructose-1,6-diphosphate (FDP) has been studied for its ability to protect tissue during hypoxia or ischemia. Recently, a clear effect of FDP on the central nervous system has raised the question whether FDP can get into the brain. FDP levels were measured in blood, brain, liver, kidney, muscle and fat after intraperitoneal administration of a single 0.5g kg-1 dose of FDP to adult male Sprague-Dawley rats. A complete time course of the levels in blood and brain was determined. The levels of FDP in the blood and brain increase simultaneously, i.e. there is no lag in the increase in the brain. The levels of FDP fall to baseline in liver, kidney, muscle and fat by 12 hours, but remain elevated in blood and brain. However, levels in the blood at 12 hours are significantly decreased from the peak levels, while those in brain are not different from the peak levels, suggesting that the kinetics of FDP in blood and brain are quite different. Stripping the endothelial cells from the brain tissue sample did not change the levels of FDP indicating that FDP is not trapped in the capillary cells. Incubation of brain slices in a solution of FDP, followed by washing, raised tissue levels of FDP indicating that FDP is taken up into cells within the brain. Finally, the experiments demonstrate a significant increase in brain levels of FDP after oral administration. These data suggest that an oral formulation of FDP might be developed for treatment of neurological disease.

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Improved brain metabolism with fructose 1-6 diphosphate during insulin-induced hypoglycemic coma

Cited by 19 publications

References 25 publications

Prevention of ischemic-hypoxic brain injury and death in rabbits with fructose-1,6-diphosphate.

Prevention of ischemic-hypoxic brain injury and death in rabbits with fructose-1,6-diphosphate.

Fructose-1,6-bisphosphate stabilizes brain intracellular calcium during hypoxia in rats.

Pharmacokinetics of fructose-1,6-diphosphate after intraperitoneal and oral administration to adult rats

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