Fructose-1, 6-bisphosphatase (FBPase), a rate-limiting enzyme involved in the pathway of gluconeogenesis, can catalyze the hydrolysis of fructose-1, 6-bisphosphate to fructose-6-phosphate. Upon inhibiting the activity of FBPase, the production of endogenous glucose can be decreased and the level of blood glucose lowered. Therefore, inhibitors of FBPase are expected to be novel potential therapeutics for the treatment of type II diabetes. Recent research efforts were reviewed in the field of developing allosteric inhibitors interacting with the AMP binding site of FBPase.
Adenosine Monophosphate ; chemistry ; Allosteric Site ; Animals ; Binding Sites ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; Enzyme Inhibitors ; chemistry ; pharmacology ; Fructose-Bisphosphatase ; antagonists & inhibitors ; chemistry ; metabolism ; Fructosediphosphates ; metabolism ; Fructosephosphates ; metabolism ; Humans

Hereditary fructose intolerance is an autosomal recessive disorder that is caused by a deficiency in fructose-1-phosphate aldolase (Aldolase B). Children can present with hypoglycemia, jaundice, elevated liver enzymes and hepatomegaly after intake of dietary fructose. Long-term intake of fructose in undiagnosed patients can result in hepatic failure or renal failure. We experienced a case of hereditary fructose intolerance presenting as recurrent hepatitis-like episodes. Detailed evaluation of her dietary habits revealed her avoidance of sweetened foods and fruits. Genetic analysis of ALDOB revealed that she is a homozygote for a novel frameshifting mutation c[758_759insT]+[758_759insT] (p.[val25 3fsX24]+[val253fsX24]). This report is the first of a Korean patient diagnosed with hereditary fructose intolerance using only molecular testing without undergoing intravenous fructose tolerance test or enzyme assay.
Child ; Enzyme Assays ; Food Habits ; Frameshift Mutation ; Fructose ; Fructose Intolerance ; Fructose-Bisphosphate Aldolase ; Fructosephosphates ; Fruit ; Hepatitis ; Hepatomegaly ; Homozygote ; Humans ; Hypoglycemia ; Jaundice ; Liver ; Liver Failure ; Renal Insufficiency

OBJECTIVEFructose-1, 6-diphosphate (FDP), serving as a cellular energy substance, has shown its roles in the treatment of hypoxic-ischemic encephalopathy and myocardial damage. The present study aimed at exploring the potentiality of the protective effect of FDP against ultrastructural damage of the hippocampus caused by febrile seizures (FS) in rats.

METHODSThirty-six 21-day-old male Sprague-Dawley rats were randomly divided into three groups: untreated FS (control), high-dose FDP-treated FS and low-dose FDP-treated FS. FS were induced by hyperthermal bath. Thirty minutes before FS induction, rats in the high-dose and low-dose FDP-treated groups received a peritoneal injection of FDP at a dosage of 50 and 25 mg per 100 g of body weight respectively, whereas the same volume of 0.9% sodium chloride solution were injected to the rats in the control group. Transmission electron microscopy was used to examine the ultrastructural pathologic changes of neurons and organelles as well as the features of synaptic morphological parameters in the hippocampal CA1 area.

RESULTSNeuronal degeneration and necrosis, mitochondria swelling, polyribosomes disaggregation from endoplasmic reticula, and golgiosomes dilation in the hippocampal CA1 area in the two FDP intervention groups were less severe compared with the control group. FDP treatment resulted in significant increases in postsynaptic density thickness (F=12.47, P<0.01), synaptic active zone length (F=14.75, P<0.01) and synaptic interface curvature (F=3.77, P<0.05), as well as a shorter interspace of neural synapses (F=7.29, P<0.01) when compared with the control group. There were no significant differences in the ultrastructural changes between the two FDP treatment groups.

CONCLUSIONSFDP can ameliorate ultrastructural damage in the hippocampus caused by FS in rats. However, further research is warranted for a reasonable and effective dosage of FDP.

Animals ; Fructosediphosphates ; therapeutic use ; Hippocampus ; ultrastructure ; Male ; Neuroprotective Agents ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Seizures, Febrile ; drug therapy ; pathology

AIMTo study the effects of sodium magnesium fructose diphosphate (SMFD) on free calcium concentration and nitric oxide synthase activity of ischemic synaptosome, so as to explore the protective mechanisms of SMFD on cerebral ischemia.

METHODSThe synaptosomes from normal rat brain were prepared by phase partition and cultured with oxygen-glucose deprivation to establish ischemic synaptosome model. The intrasynaptosomal free calcium concentration and nitric oxide synthase activity were detected separately after the synaptosomes were co-incubated with SMFD (1.3 mmol.L-1) or fructose-1, 6-diphosphate (FDP, 4.0 mmol.L-1) for 60 min.

RESULTSSMFD decreased the free calcium concentration and reduced the activity of nitric oxide synthase (NOS) of ischemic synaptosomes. Its effects were more powerful than those of FDP.

CONCLUSIONSMFD may protect neurons from ischemic injury by preventing intracellular Ca2+ overload and inhibiting the activity of nitric oxide synthase.

Animals ; Brain Ischemia ; enzymology ; metabolism ; Calcium ; metabolism ; Chelating Agents ; pharmacology ; Fructosediphosphates ; pharmacology ; Magnesium ; chemistry ; Male ; Nitric Oxide Synthase ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Sodium ; chemistry ; Synaptosomes ; metabolism

OBJECTIVEFebrile seizure (FS) is a pediatric emergency. The reiterative attacks of FS may result in brain damage to various extents. Fructose-1,6-diphosphate, serving as a cellular energy substance, has been applied to clinical practice for many years and has shown its importance in adjuvant treatment of diseases with myocardial damage. This study aimed to explore the potentiality of protecting rats' brain damage caused by febrile seizure with fructose-1,6-diphosphate (FDP).

METHODSThirty 21-day-old male Sprague-Dawley (SD) rats were randomly divided into febrile seizure group (FS), sodium chloride solution (NS) control group and FDP intervention group (FD). Febrile seizure was induced by hyperthermal bath at 45 degrees C in the present study. No intervention treatment was given to rats in FS group before febrile seizure. Thirty minutes before febrile seizures, rats in FD group were given peritoneal injection of FDP at a dose of 25 mg per 100 g of body weight, whereas the same volume of 0.9% sodium chloride solution was injected into peritoneum of rats in NS group. Manifestations of seizure and differences in seizure latency, duration of seizure and seizure severity were observed in all the 3 groups. Samples of rat brain were prepared for electron microscopy in order to understand the characteristics of the ultrastructural changes in mitochondria, interspace of neuronal synapses and neurons of hippocampal region CA(1).

RESULTSData collected from this study indicated that peritoneal injection of FDP at 25 mg per 100 grams of body weight 30 minutes before febrile seizures could result in improvement of the clinical manifestation of the rats caused by febrile seizures. Specifically speaking, the seizure latency was prolonged, the duration of seizures was shortened and severity of seizure was reduced. Analysis of variance and q-test on the data collected from the 3 groups revealed that there were significant differences between FD group and the other two groups (P < 0.05), yet no significant difference was found between FS group and NS group (P > 0.05). Electron microscopic observations on brain specimens revealed that FDP could relieve mitochondrial degeneration and edema. FDP could also reduce neuronal degeneration and necrosis in hippocampal region CA(1) (the percentages of neuronal degeneration and necrosis in the 3 groups were respectively 13% for FD group, 28% for FS group and 30% for NS group). There was a significant difference between FD group and the other two groups (P < 0.05), FDP treatment could prevent interspace of neuronal synapses from enlarging (the mean interspace was 6.47 +/- 0.37 micro m for FD group, 7.60 +/- 0.36 micro m for FS group and 7.53 +/- 0.40 micro m for NS group. The difference between FD group and the other two groups was significant (P < 0.01).

CONCLUSIONFDP could lead to prolonged seizure latency, shorter duration of seizures and mitigation of seizures severity. FDP could also reduce neuronal degeneration and necrosis and prevent the interspace of neuronal synapses from enlarging in hippocampal region CA(1). The present study suggests that FDP can protect brain of rat from damages caused by febrile seizures.

Animals ; Brain ; drug effects ; pathology ; Disease Models, Animal ; Fructosediphosphates ; therapeutic use ; Male ; Neuroprotective Agents ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Seizures, Febrile ; drug therapy ; Treatment Outcome

OBJECTIVETo investigate the effects of strontium fructose 1,6-diphosphate (FDP-Sr) on the multiglycosides of tripterygium wilfordii Hook. f. (GTW)-induced oligozoospermia in male rats.

METHODSForty SD male rats were randomly divided into 3 groups: model (n=10), FDP-Sr (n=10), and control (n=10). The model rats received intragastric administration of GTW at 30 mg/(kg x d) for 40 days to induce oligozoospermia, the rats of the FDP-Sr group orally administered FDP-Sr at 200 mg/(kg x d) for 30 days after GTW induction, while the control rats given but distilled water. Then we obtained the gonad indexes involving the testis, epididymis, preputial gland and seminal vesicle, and determined the count and motility of epididymal sperm, testicular pathomorphology, serum testosterone level and activities of succinodehydrogenase (SDH), lactate dehydrogenase (LDH) and acid phosphatase (ACP) in the testis.

RESULTSThe indexes of the testis and seminal vesicle in the control, model and FDP-Sr groups were (0.71 +/- 0.04) and (0.29 +/- 0.04)%, (0.37 +/- 0.04) and (0.25 +/- 0.05)%, and (0.45 +/- 0.07) and (0.31 +/- 0.06)%, respectively; the epididymal sperm counts were (59.87 +/- 11.28), (11.06 +/- 2.53) and (20.95 +/- 4.98) x 10(6)/ml; the serum testosterone levels were (85.31 +/- 7.41), (65.33 +/- 2.90) and (75.32 +/- 5.34) ng/L; and the activities of ACP, LDH and SDH were (95.64 +/- 19.27), (9574.73 +/- 3 578.06) and (6.39 +/- 1.93) U/g prot, (58.42 +/- 12.38), (4820.77 +/- 1 535.22) and (3.48 +/- 0.91) U/gprot, and (83.74 +/- 21.30), (7649.01 +/- 3 123.02) and (5.59 +/- 1.75) U/g prot. All the parameters above were significantly increased in the FDP-Sr group as compared with the GTW models (P < 0.05). Besides, FDP-Sr treatment significantly alleviated the injury of the testicular seminiferous epithelium.

CONCLUSIONFDP-Sr can alleviate GTW-induced oligozoospermia, which is closely related with its improvement of testicular function.

Animals ; Fructosediphosphates ; therapeutic use ; Glycosides ; adverse effects ; Male ; Oligospermia ; chemically induced ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Strontium ; therapeutic use ; Tripterygium ; chemistry

OBJECTIVETo study the dose- and time-dependent protective effects and the synergistic effects of nimodipine (NMDP) and fructose-1,6-diphosphate (FDP) against cerebral damage induced by acute carbon monoxide (CO) poisoning in mice.

METHODSMale mice were exposed to CO 170 mL/kg, i.p. After CO intraperitonealy exposure, mortality of mice, change in memory function estimated by passive avoidance test, the pathomorphologic observation of brain tissue slices, as well as changes of activities of monoamine oxidase (MAO)-B and Ca(2+)-Mg(2+)-ATPase in cerebral tissue were studied. In dose-dependent protective effect study, NMDP (10.6, 5.3, 2.7 mg/kg) and FDP (2.6, 1.3, 0.67 g/kg) was injected ip, respectively 15 min after CO exposure. To study the time-effect relationship of drugs, NMDP (5.3 mg/kg) and FDP (1.3 g/kg) were administered ip respectively 15 minutes, 45 minutes and 120 minutes after CO exposure. The combination of NMDP (2.7 mg/kg) and FDP (0.67 g/kg) was administered ip15 minutes, 45 min and 120 minutes after CO exposure to study the synergism of the two drugs.

RESULTSEither NMDP (10.6, 5.3 mg/kg) or FDP (2.6, 1.3 g/kg) administered ip within 15 minutes after CO exposure significantly decreased the impairment of memory function and mortality rate induced by CO, inhibited the decrease of Ca(2+)-Mg(2+)-ATPase activity, blunted the rising of MAO-B activity and prevented the delayed hippocampal neuronal death in poisoning mice. To our surprise, the combined use of NMDP (2.7 mg/kg) and FDP (0.67 g/kg) within 15 minutes after CO exposure had similar effects to that in NMDP (10.6, 5.3 mg/kg) and FDP (2.6, 1.3 g/kg).

CONCLUSIONSThese results suggest that the impairment of CO on brain can be attenuated if NMDP or FDP are administered sufficiently and quickly as soon as possible after CO exposure and there exists a synergism of FDP and NMDP against CO poisoning damage.

Animals ; Brain Damage, Chronic ; prevention & control ; Calcium Channel Blockers ; therapeutic use ; Carbon Monoxide Poisoning ; prevention & control ; Dose-Response Relationship, Drug ; Drug Synergism ; Fructosediphosphates ; therapeutic use ; Male ; Mice ; Neuroprotective Agents ; therapeutic use ; Nimodipine ; therapeutic use ; Time Factors

OBJECTIVETo investigate whether the protective effect of therapy with different combined neuroprotectant agents was better than that of single agent on focal cerebral ischemia.

METHODSThe right middle cerebral artery in the rats was occluded with suture occlusion technique. The rats were divided into five groups treated with FDP (50 mg/kg, n = 10), MK-801 (1 mg/kg, n = 10) and NAC (150 mg/kg, n = 10) singly, or in combination, respectively, by intraperitoneal infusion 30 minutes after vessel occlusion. The rats were weighed and assessed neurologically, based on a 5-point scale, six and 24 hours after focal cerebral ischemia. The expression of anti-apoptotic protein bcl-2 was observed with SDS-PAGE protein electrophoresis and Western blot technique.

RESULTThe optical density of bcl-2 increased more distinctly in the rats treated with combined neuroprotective agents than that with any single agent six and 24 hours after cerebral ischemia, with a statistically significant difference (P < 0.05).

CONCLUSIONSTreatment with combined neuroprotectant agents could un-regulate the anti-apoptotic protein bcl-2 more distinctly than that with any single agents. Combined use of neuroprotectants might be more effective than that of single agent in protecting rats' brain from ischemia.

Acetylcysteine ; administration & dosage ; Actins ; analysis ; Animals ; Brain Ischemia ; drug therapy ; metabolism ; Dizocilpine Maleate ; administration & dosage ; Drug Therapy, Combination ; Fructosediphosphates ; administration & dosage ; Male ; Molecular Weight ; Neuroprotective Agents ; administration & dosage ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Rats ; Rats, Wistar

AIMTo investigate the protective role of HO/CO systems in IL-1beta induced islest apoptosis and to explore the mechanisms of the protective effect of fructose-1, 6-disphosphate (FDP).

METHODSThe pancreases of the rats were removed to collect islets cells. The cells were incubated with IL-1beta with/or FDP. Cell activity, insulin secretion, HO-1 activity, CO content and apoptotic percentage were detected.

RESULTSHO-1 activity and CO content of the normal control group were low. IL-1beta induced a significant decrease of cell activity and insulin release, flow cytometry analysis showed that apoptotic percentage of islet cells remarkably increased following the addition of IL-1beta, FDP obviously improved the islets cellular activity damaged by IL-1beta, and basic amount of insulin secretion and stimulated by high glucose were improved (P < 0.01). Content of CO and activity of HO-1 were higher in the IL-1beta group than the normal control group (P < 0.05), and there were significant differences between the FDP groups and IL-1beta group. FDP decreased cell apoptotic percentage. Activities of HO-1 and content of CO were higher than that in the IL-1beta group (P < 0.01).

CONCLUSIONFDP can attenuate the IL-1beta induced apoptosis of cultured beta cells, the mechanism of which may be improved HO-1 activity and CO content.

Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Carbon Monoxide ; metabolism ; Cells, Cultured ; Female ; Fructosediphosphates ; pharmacology ; Heme Oxygenase (Decyclizing) ; metabolism ; physiology ; Insulin ; secretion ; Interleukin-1beta ; antagonists & inhibitors ; pharmacology ; Islets of Langerhans ; cytology ; Male ; Rats ; Rats, Wistar

OBJECTIVE: To investigate the effect of fructose-1,6-diphosphete(FDP) on myocardial preservation in pulmonary operations. METHODS: One hundred and six patients undergoing selective pulmonary lobectomy or segmentectomy were randomly divided into 2 groups with 53 patients each. FDP 200 mg/kg was infused intravenously before anesthesia in the FDP group, while 5% glucose with the same volume was given instead of FDP in the control group. ECGs were monitored from before the anesthesia to 72 h after the operation;the time and type of arrhythmia were recorded. Blood samples were taken before the operation (T0), immediately after the operation(T1), at 24 h(T2),48 h(T3)and 72 h(T(4)) after the operation to determine plasma creatine kinase isoenzyme MB(CK-MB) and cardiac troponin I(cTnI) concentrations. RESULTS: The incidence of arrhythmia in FDP group (35 times) was significantly lower than that in the control group(67 times). The incidence of all types of arrhythmia in the FDP group was also significantly lower than that in the control group. The concentrations of CK-MB and cTnI in the FDP group were significantly lower than those in the control group at T1, T2, T3, and T4. CONCLUSION FDP is effective for myocardial preservation in pulmonary operations.
Aged ; Anti-Arrhythmia Agents ; therapeutic use ; Arrhythmias, Cardiac ; etiology ; prevention & control ; Creatine Kinase, MB Form ; blood ; Female ; Fructosediphosphates ; therapeutic use ; Humans ; Male ; Middle Aged ; Pneumonectomy ; adverse effects ; Troponin I ; blood