Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of cyclosporin A, a highly effective immunosuppressant, was investigated on hyperoxaluric rats with and without vitamin E pretreatment. Hyperoxaluria was induced by oral feeding of 3% ammonium oxalate in water for 3 days. Cyclosporin A (50 mg/kg body wt.) was administered for 3 days. Pretreatment with vitamin E (50 mg/100 g body wt., once a week for 3 weeks) was carried out before the administration of cyclosporin A and ammonium oxalate. Nonenzymatic ascorbate-induced lipid peroxidation was increased to 1.55-fold in either cyclosporin A-administered or hyperoxaluric rat kidney and liver when compared to control. The lipid peroxidation was further elevated to 1.9-fold when both cyclosporin A and ammonium oxalate were coadministered. The activities of renal and hepatic ATPase, glucose-6-phosphatase as well as the concentrations of thiols were decreased significantly (p < 0.001) when cyclosporin A was administered under hyperoxaluric condition. On pretreatment with vitamin E the cyclosporin A-induced biochemical changes observed in the presence of hyperoxaluria were abolished.
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PMID:Effect of cyclosporin A on tissue lipid peroxidation and membrane bound phosphatases in hyperoxaluric rat and the protection by vitamin E pretreatment. 935 65

The purpose of this study was to determine the effects of taurine supplementation on both hepatic morphological changes and the extent of hepatic lipid peroxidation and membrane disintegration during rat hepatocarcinogenesis. Sprague Dawley rats were fed high fat diets containing 15% corn oil and were maintained on drinking water with or without 1% taurine. Two weeks after the appropriate feeding regimen, hepatocarcinogenesis was induced by a modification of the Solt and Farber method. This involved a 8 week protocol, including diethylnitrosamine initiation, 3 weeks of 2-acetylaminofluorene feeding and finally a 70% partial hepatectomy. Morphological changes of the hepatocyte were observed by transmission electron microscopy (TEM). Hepatocytes of the carcinogen-treated rat not exposed to taurine contained normal nuclei, but the endoplasmic reticulum (ER) and the mitochondria (Mi) were almost destroyed. By contrast, although the hepatocytes from the taurine supplemented group contained some irregular contour nuclei, the ER and Mi were normal. In the carcinogen-treated groups, lipid peroxidation was decreased because of the activation of several detoxifying enzymes. Glutathione S-transferase (GST) activity increased in the carcinogen-treated groups but less so in the group supplemented with taurine before treatment with the carcinogen. In the group supplemented with taurine prior to treatment with the carcinogen, glutathione peroxidase (GPx) activity was higher than in the carcinogen-treated group lacking taurine exposure. Consistent with the severe destruction to the membrane in the carcinogen-treated rats, hepatic glucose-6-phosphatase (G6Pase) activity, an index of membrane stability, was also decreased. However, both the fall in G6Pase activity and the degree of membrane damage was reduced in the carcinogen-treated animals receiving oral taurine. These results suggest that taurine appears to inhibit lipid peroxidation, to alter the activity of the defense enzymes and to protect the liver against membrane disintegration during rat hepatocarcinogenesis.
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PMID:Taurine protects the liver against lipid peroxidation and membrane disintegration during rat hepatocarcinogenesis. 963 21

Preneoplastic liver foci and neoplasms of different morphological phenotypes were induced in rats with N-nitrosomorpholine (NNM; 120 mg/l in drinking water for 7 weeks) and the peroxisome proliferator dehydroepiandrosterone (DHEA; 0.6% in the diet for up to 84 weeks). Preneoplastic glycogen storage foci (GSF) occurred mainly upon treatment with NNM, and amphophilic cell foci (APF) were mainly observed in rats treated with DHEA alone or in combination with NNM. The 2 types of lesions belong to 2 different cellular lineages, the glycogenotic/basophilic lineage and the amphophilic lineage, which are characterized by distinct patterns of alterations in key enzymes of energy metabolism. Whereas in GSF enzymes of glucose metabolizing pathways were modified (increase in glucose-6-phosphate dehydrogenase and pyruvate kinase, decrease in glucose-6-phosphatase), APF mainly demonstrated alterations in mitochondrial enzymes (increase in cytochrome c oxidase, succinate dehydrogenase and glycerol-3-phosphate dehydrogenase) and, to a lower extent, in peroxisomal enzymes (increase in peroxisomal hydratase and acyl-CoA oxidase). The alterations in enzyme expression reflect an insulinomimetic effect in GSF and a thyromimetic effect in APF. Neoplasms resulting from APF show a more differentiated phenotype than those arising from GSF. We suggest that the different and in many aspects opposite effects of the 2 carcinogens on key enzymes of distinct pathways of energy metabolism modulate the process of neoplastic liver cell transformation and result in phenotypically different preneoplasias and neoplasias reflecting different cellular lineages.
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PMID:Differential expression of key enzymes of energy metabolism in preneoplastic and neoplastic rat liver lesions induced by N-nitrosomorpholine and dehydroepiandrosterone. 964 43

The characterization of the structure of mumbaistatin (1), an effective inhibitor of the glucose-6-phosphatase system (EC 3.1.3.9), is reported. Isolation of mumbaistatin from cultures of Streptomyces sp. DSM 11641 was achieved by anion-exchange and reversed-phase chromatography. The acid-labile inhibitor was methylated for the structure determination. Single-crystal X-ray structure analysis of a triply methylated dehydration product, C31H24O11, revealed the structure of an aromatic dispirodiketal (2), a compound containing a previously undescribed ring system. Extensive 2D-NMR experiments with mumbaistatin and with the methylation products showed that mumbaistatin itself possesses the hydroxydiketodicarboxylic acid structure 1, C28H20O12, which, in the presence of acid or upon activation through methyl ester formation, undergoes self-condensation with loss of water to the dispirodiketal form (2). Mumbaistatin is an anthraquinone derivative, whose open-chain diketo form acts as a specific and powerful inhibitor of glucose-6-phosphate translocase: IC50=5 nM. The activity towards the same enzyme of the cyclized dispirodiketal derivatives is roughly one thousand times lower.
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PMID:The chemical structure of mumbaistatin, a novel glucose-6-phosphate translocase inhibitor produced by Streptomyces sp. DSM 11641. 1142 60

Glycogen storage disease type Ib is an autosomal recessive inherited metabolic disorder resulting from deficiency of the microsomal glucose-6-phosphatase enzyme system. Six patients (three of which were treated with granulocyte colony stimulating factor) suffering from this disease were examined using image guided localized proton magnetic resonance (MR) spectroscopy. The relative signal intensities of water and lipid protons of the lumbar spine were determined. Comparison was made with iliac crest biopsies in the glycogen storage disease type Ib patients and localized proton MR spectroscopic values of the lumbar spine obtained by thirteen healthy volunteers. The data demonstrate for the first time that hypercellularity and myeloid hyperplasia in subjects with glycogen storage disease type Ib due to functionally impaired leucocytes results in a strongly increased water proton signal with a very low or absent lipid signal in localized proton MR spectroscopy. Upon granulocyte colony stimulating factor treatment, the water proton signal in the lumbar spine is not further augmented.
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PMID:Proton MR spectroscopy of the lumbar spine in patients with glycogen storage disease type Ib. 1220 90

In the present study, we have examined the possible mechanism of the hypoglycemic action of the semi-purified fractions of an ethanolic extract of Averrhoa bilimbi Linn (Oxalidaceae) leaves (ABe) in streptozotocin-diabetic male Sprague-Dawley (SD) rats. The ABe was partitioned with water and butanol to yield a butanol-soluble fraction (BuF) and a water-soluble fraction (AF). The AF was further partitioned with ethyl acetate and hexane to obtain ethyl acetate (EF) and hexane (HF) soluble fractions. The hypoglycemic property of each fraction was assessed by the oral glucose tolerance test (OGTT) at a dose of 125-mg/kg-body weight in streptozotocin (STZ)-diabetic rats (STZ 60 mg/kg i.p.). Fractions AF, BuF and the reference drug metformin (500 mg/kg body weight), produced significant blood glucose-lowering effect in the diabetic rats when compared to the vehicle (distilled water). In the long-term study, the diabetic rats were randomly divided into 4 groups and treated orally by gavage with vehicle, AF (125 mg/kg body weight), BuF (125 mg/kg body weight), and metformin (500 mg/kg body weight) respectively twice a day for 14 days. On day 7 and day 14, AF and BuF, like the reference drug, metformin, lowered the fasting blood glucose concentration significantly (P < 0.05) when compared with the vehicle. The serum insulin level was significantly increased in the AF-treated rats only on day 14 when compared to that in the vehicle-treated rats on day zero (P < 0.05). The serum insulin level in BuF-treated rats was also significantly higher (P < 0.05) on both day 7 and day 14 compared to that on day zero. Hepatic glucose-6-phosphatase activity was significantly lower (P<0.05) in AF- and metformin-treated groups, but not in BuF-treated groups, compared to that in vehicle-treated group. However, there was no change in hepatic glycogen content in AF-, BuF- and metformin-treated group compared to the vehicle-treated group. These results indicate that AF is more potent than BuF in the amelioration of hyperglycemia in STZ-diabetic rats and is a potential source for the isolation of new orally active agent(s) for anti-diabetic therapy.
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PMID:The mechanism of hypoglycemic action of the semi-purified fractions of Averrhoa bilimbi in streptozotocin-diabetic rats. 1181 98

Vanadium treatment normalizes plasma glucose levels in streptozotocin-diabetic rats in vivo, but the mechanism(s) involved are still unclear. Here, we tested the hypothesis that the in vivo effects of vanadium are mediated by changes in gluconeogenesis. Diabetic rats were treated with bis(maltolato)oxovanadium(IV) (BMOV) in the drinking water (0.75-1 mg/ml, 4 wk) or, for comparison, with insulin implants (4 U/d) for the final week of study. As with insulin, BMOV lowered plasma glucose and normalized phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) mRNA in the liver and kidney of diabetic rats. To determine the importance of reducing hyperglycemia per se, diabetic rats were treated either with a single ED(50) dose of BMOV (0.1 mmol/kg, ip) or with phlorizin (900 mg/kg.d, 5 d). BMOV rapidly restored PEPCK and G-6-Pase mRNA and normalized plasma glucose in responsive (50%) diabetic rats but had no effect on the nonresponsive hyperglycemic rats. Phlorizin corrected plasma glucose but had no effect on PEPCK mRNA and only partially normalized G-6-Pase mRNA. In conclusion, 1) BMOV inhibits PEPCK mRNA expression and activity by rapid mechanisms that are not reproduced simply by correction of hyperglycemia; and 2) BMOV inhibits G-6-Pase expression by complex mechanisms that depend, in part, on correction of hyperglycemia.
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PMID:Mechanisms by which bis(maltolato)oxovanadium(IV) normalizes phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression in streptozotocin-diabetic rats in vivo. 1244 91

Electron-dense granules (EDGs) are singular structures found in the tissues of several vertebrate and invertebrate organisms. Two types of EDGs were observed in hepatopancreatic cells of the crab Ucides cordatus: (1) a non-mineralized EDG, found mainly inside vacuoles, which reacted positively to acid phosphatase and D-amino acid oxidase, possibly formed by degradation of lipid membranes, and (2) a mineralized EDG surrounded by endoplasmic reticulum membranes that gave a positive reaction for glucose-6-phosphatase. In this study we show the fine structure and composition of the mineralized EDGs using cytochemistry, analytical transmission electron microscopy and field-emission scanning electron microscopy. They are formed of microvesicle-like structures that are arranged in concentric spherical layers in the most mineralized portions of the granule. Analytical microscopy of mineralized EDGs indicated that they are composed of amorphous calcium-magnesium phosphate. Isolated EDGs treated with NaOCl lose several elements, including P, when compared with EDGs treated with deionized water. Removal of the organic matrix by NaOCl induced marked changes in the mineralized EDGs, showing that the organic matrix plays an important role in its elemental composition and structure.
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PMID:Enzymatic, analytical and structural aspects of electron-dense granules in cells of Ucides cordatus (Crustacea, Decapoda) hepatopancreas. 1248 90

To determine the mechanism(s) by which insulin inhibits endogenous glucose production (EGP) in nondiabetic humans, insulin was infused at rates of 0.25, 0.375, or 0.5 mU. kg(-1). min(-1) and glucose was clamped at approximately 5.5 mmol/l. EGP, gluconeogenesis, and uridine-diphosphoglucose (UDP)-glucose flux were measured using [3-(3)H]glucose, deuterated water, and the acetaminophen glucuronide methods, respectively. An increase in insulin from approximately 75 to approximately 100 to approximately 150 pmol/l ( approximately 12.5 to approximately 17 to approximately 25 microU/ml) resulted in progressive (ANOVA; P < 0.02) suppression of EGP (13.1 +/- 1.3 vs. 11.7 +/- 1.03 vs. 6.4 +/- 2.15 micromol x kg(-1) x min(-1)) that was entirely due to a progressive decrease (ANOVA; P < 0.05) in the contribution of glycogenolysis to EGP (4.7 +/- 1.7 vs. 3.4 +/- 1.2 vs. -2.1 +/- 1.3 micro mol x kg(-1) x min(-1)). In contrast, both the contribution of gluconeogenesis to EGP (8.4 +/- 1.0 vs. 8.3 +/- 1.1 vs. 8.5 +/- 1.3 micro mol x kg(-1) x min(-1)) and UDP-glucose flux (5.0 +/- 0.4 vs. 5.0 +/- 0.3 vs. 4.0 +/- 0.5 micro mol x kg(-1) x min(-1)) remained unchanged. The contribution of the direct (extracellular) pathway to UDP-glucose flux was minimal and constant during all insulin infusions. We conclude that higher insulin concentrations are required to suppress the contribution of gluconeogenesis of EGP than are required to suppress the contribution of glycogenolysis to EGP in healthy nondiabetic humans. Since suppression of glycogenolysis occurred without a decrease in UDP-glucose flux, this implies that insulin inhibits EGP, at least in part, by directing glucose-6-phosphate into glycogen rather than through the glucose-6-phosphatase pathway.
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PMID:Higher insulin concentrations are required to suppress gluconeogenesis than glycogenolysis in nondiabetic humans. 1294 59

Early effects of cadmium (Cd) on the structure and function of the kidney were studied in an experimental model using rats intoxicated with Cd at the levels of 5 and 50 mg Cd/l drinking water. The effect of Cd was evaluated histopathologically and biochemically. Damage to the cellular structures was assessed on the basis of histoenzymatic analyses of the activity and localization of indicator enzymes (succinate dehydrogenase, lactate dehydrogenase, glucose-6-phosphatase, Mg(2+)-dependent adenosine triphosphatase and acid phosphatase). The histochemical observations indicate that Cd causes damage to the organization and function of the nephron. Several structures, i.e. endoplasmic reticulum, mitochondrion, lysosome, cellular and intracellular membrane, as well as their biological functions, i.e. aerobic and anaerobic respiration, transport functions and biochemical processes taking place in the endoplasmic reticulum, were affected. The cytotoxic action of Cd occurs mainly in the tubules and partially also in the glomeruli. The results clearly indicate that Cd damages kidney structurally and functionally even at a relatively low level (5 mg/l) corresponding to human environmental exposure, and they confirm our previous hypothesis that the threshold for the kidney effects of Cd is less than 4.08+/-0.33 microg/g kidney wet weight and higher than 2.40+/-0.15 microg/g. The target for Cd action in the kidney is the tubules (proximal convoluted tubules and straight tubules), and disturbance in their function is the main toxic effect of Cd. Renal glomeruli are also injured, but only partially, whereas in other parts of the nephron the damage is slight. The results, together with observations reported in the first paper of the study, incline us to conclude that humans environmentally exposed to Cd are at risk of tubular damage.
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PMID:Changes in the structure and function of the kidney of rats chronically exposed to cadmium. II. Histoenzymatic studies. 1499 81


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