Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.9 (glucose-6-phosphatase)
3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human tumor necrosis factor-alpha (TNF) injection in mice was associated with a reduced blood glucose level, already manifest 6 hours following cytokine administration. Insulin levels were not affected. Glycogen content was decreased in a dose-dependent and time-response manner. The activity of glucose-6-phosphatase (G6Pase) was already reduced 6 hours after TNF injection and was sustained 12 hours afterward. Phosphoenolpyruvate carboxykinase (PEPCK) activity was not affected initially (6 hours after injection), but a 50% reduction was observed 12 hours following cytokine administration compared with levels in fasting controls. Both liver G6Pase and PEPCK mRNAs were markedly reduced due to an inhibition of the transcriptional rate. A direct inhibitory effect of TNF on G6Pase promoter activity was demonstrated using HuH-7 cells transiently transfected with G6Pase promoter, fused to a reporter gene.
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PMID:Tumor necrosis factor inhibits the transcriptional rate of glucose-6-phosphatase in vivo and in vitro. 916 Aug 27

Mice bearing interleukin-6 (IL-6)-secreting tumor were used to study the chronic effect of IL-6 on carbohydrate metabolism. Mice were injected with allogeneic tumor cells transduced with the murine IL-6 gene. Serum IL-6 levels were correlated exponentially with tumor weight. Secretion of IL-6 from the developed tumors was associated with decreased food consumption, reduced body weight, and reduced blood glucose levels. Insulin levels did not change, and 2-deoxyglucose uptake was not affected in most tissues examined. A significant increase of 2-deoxyglucose uptake was measured in the liver. Glycogen content in the liver determined 0, 6, 12, and 18 days after tumor inoculation was 42, 23, 12, and 3 mg/g, respectively. The activity of phosphoenolpyruvate carboxykinase was not affected. The activity of glucose-6-phosphatase (G-6-Phase) determined 6, 12, and 18 days after tumor injection was 84, 70, and 50% of G-6-Pase activity in pair-fed mice bearing nonsecreting tumors, respectively. G-6-Pase mRNA levels were markedly reduced due to inhibition of G-6-Pase gene transcriptional rate.
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PMID:Interleukin-6 secretion in mice is associated with reduced glucose-6-phosphatase and liver glycogen levels. 927 78

This study was conducted to identify the nature of a glycogen-associated compound that had been shown to inhibit glucose-6 phosphatase in vitro. Glycogen was purified from the liver of fed rats by potassium hydroxyde digestion and ethanol precipitation. It inhibited glucose-6 phosphatase in microsomes isolated from rats deprived of food for 48 h. Two glycogen-associated fractions were purified by anion-exchange chromatography on DOWEX 1 (200-400 mesh). These fractions inhibited microsomal glucose-6-phosphatase activity in vitro (80 +/- 2 and 76 +/- 3% of control, respectively). After chromatography, glycogen was no longer inhibitory (101 +/- 3% of control). Because glycogen is associated with endoplasmic reticulum membranes in the liver, we tested the hypothesis that lipids could be involved in the inhibitory process. Lipids were extracted from glycogen by Folch's method and analyzed by thin-layer chromatography and gas chromatography. The glycogen-associated fractions did not contain complex lipids but contained unsaturated fatty acids, which had been shown previously to inhibit glucose-6-phosphatase in vitro. Because the concentration of unsaturated fatty acids in both fractions quantitatively accounted for the inhibition of glucose-6 phosphatase observed, and because noninhibitory chromatographed glycogen reconstituted with equivalent amounts of pure unsaturated fatty acids inhibited the enzyme as glycogen did, we conclude that unsaturated fatty acids likely constitute the glycogen-associated compound that inhibits glucose-6 phosphatase activity.
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PMID:Unsaturated fatty acids associated with glycogen may inhibit glucose-6 phosphatase in rat liver. 940 76

Glycogen-storage disease type 1 (GSD-1), also known as "von Gierke disease," is caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase) activity. There are four distinct subgroups of this autosomal recessive disorder: 1a, 1b, 1c, and 1d. All share the same clinical manifestations, which are caused by abnormalities in the metabolism of glucose-6-phosphate (G6P). However, only GSD-1b patients suffer infectious complications, which are due to both the heritable neutropenia and the functional deficiencies of neutrophils and monocytes. Whereas G6Pase deficiency in GSD-1a patients arises from mutations in the G6Pase gene, this gene is normal in GSD-1b patients, indicating a separate locus for the disorder in the 1b subgroup. We now report the linkage of the GSD-1b locus to genetic markers spanning a 3-cM region on chromosome 11q23. Eventual molecular characterization of this disease will provide new insights into the genetic bases of G6P metabolism and neutrophil-monocyte dysfunction.
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PMID:The gene for glycogen-storage disease type 1b maps to chromosome 11q23. 946 34

To elucidate interactions between the glucose transport system and hepatic glucose production in the tumour-bearing state, glycogen storage, expression of glucose transporter isoform 2 (Glut 2) and activities of glucose-6-phosphatase (G-6-Pase) and hexokinase were histochemically examined in hepatocytes of tumour-bearing rats. Five male F344 rats, subcutaneously inoculated with methylcholanthrene (MCA)-induced sarcoma cells were compared with five pair-fed animals and four ad libitum fed controls. Glycogen storage was markedly decreased in liver cells of tumour-bearing rats compared to in those of control animals. Glut 2 immunoreactivity was uniformly seen in the cellular membrane of hepatocytes from control animals. In rats bearing sarcoma, the staining intensity was significantly decreased, suggesting that Glut 2 with its bi-directional transport capacity was down-regulated in the tumour-bearing state. Positive staining for hexokinase activity was located in the perivenous area in livers from control animals and was more diffusely located and more intense in livers from tumour-bearing animals. G-6-Pase activity, limited to the peripheral area in livers from controls, extended to the intermediate area and had stronger reactivity in livers from tumour-bearing animals. In the tumour-bearing cachectic condition, glucose may be partially consumed by a futile cycle, hepatic metabolic zonation was disturbed, and the release of glucose from the liver may not be mediated by a facilitative glucose transporter-2.
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PMID:Alteration in immunoexpression of glucose transporter 2 in liver of tumour-bearing rats. 961 47

Glycogen-storage diseases type I (GSD type I) are due to a deficiency in glucose-6-phosphatase, an enzymatic system present in the endoplasmic reticulum that plays a crucial role in blood glucose homeostasis. Unlike GSD type Ia, types Ib and Ic are not due to mutations in the phosphohydrolase gene and are clinically characterized by the presence of associated neutropenia and neutrophil dysfunction. Biochemical evidence indicates the presence of a defect in glucose-6-phosphate (GSD type Ib) or inorganic phosphate (Pi) (GSD type Ic) transport in the microsomes. We have recently cloned a cDNA encoding a putative glucose-6-phosphate translocase. We have now localized the corresponding gene on chromosome 11q23, the region where GSD types Ib and Ic have been mapped. Using SSCP analysis and sequencing, we have screened this gene, for mutations in genomic DNA, from patients from 22 different families who have GSD types Ib and Ic. Of 20 mutations found, 11 result in truncated proteins that are probably nonfunctional. Most other mutations result in substitutions of conserved or semiconserved residues. The two most common mutations (Gly339Cys and 1211-1212 delCT) together constitute approximately 40% of the disease alleles. The fact that the same mutations are found in GSD types Ib and Ic could indicate either that Pi and glucose-6-phosphate are transported in microsomes by the same transporter or that the biochemical assays used to differentiate Pi and glucose-6-phosphate transport defects are not reliable.
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PMID:A gene on chromosome 11q23 coding for a putative glucose- 6-phosphate translocase is mutated in glycogen-storage disease types Ib and Ic. 975 26

Glycogen storage diseases type 1 (GSD 1) are a group of autosomal recessive disorders characterized by impairment of terminal steps of glycogenolysis and gluconeogenesis. Mutations of the glucose-6-phosphatase gene are responsible for the most frequent form of GSD 1, the subtype 1a, while mutations of the glucose-6-phosphate transporter gene (G6PT) have recently been shown to cause the non 1a forms of GSD, namely the 1b and 1c subtypes. Here, we report on the analysis by single-stranded conformation polymorphism (SSCP) and/or DNA sequencing of the exons of the G6PT in 14 patients diagnosed either as affected by the GSD 1b or 1c subtypes. Mutations in the G6PT gene were found in all patients. Four of the detected mutations were novel mutations, while the others were previously described. Our results confirm that the GSD 1b and 1c forms are due to mutations in the same gene, i.e. the G6PT gene. We also show that the same kind of mutation can be associated or not with evident clinical complications such as neutrophil impairment. Since no correlation between the type and position of the mutation and the severity of the disease was found, other unknown factors may cause the expression of symptoms, such as neutropenia, which dramatically influence the severity of the disease.
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PMID:Mutations in the glucose-6-phosphate transporter (G6PT) gene in patients with glycogen storage diseases type 1b and 1c. 1051 30

Glycogen storage diseases (GSDs) or glycogenoses comprise several rare inherited diseases caused by abnormalities of the enzymes that regulate the synthesis or degradation of glycogen. We report on a male patient with type Ia GSD (GSD Ia) who was followed-up for more than 20 years. He had been diagnosed with GSD Ia based on biochemical tests and the glucose-6-phosphatase (G6Pase) enzyme assay from a liver biopsy at 6 years old, due to problems of hepatomegaly, growth retardation, and recurrent hypoglycemic episodes. The introduction of uncooked cornstarch improved his quality of life only in the first 8-year follow-up period. At 17 years old, gouty arthritis with multiple tophi and generalized xanthomatosis developed. Later, hepatocellular adenoma, nephrolithiasis, and gastrointestinal bleeding occurred at the age of 20, 23, and 24 years, respectively. At 26 years old, he suffered from acute renal failure and polyradiculoplexopathy. The problem of delayed puberty persisted. The story of this patient illustrates the multisystemic nature of GSD Ia and highlights the need for careful dietary therapy and long-term follow-up.
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PMID:A 20-year follow-up of a male patient with type Ia glycogen storage disease. 1284 28

Tolbutamide and carbutamide given orally to fasted rats cause a rise in the liver glycogen content 1(1/2) to 3(1/2) hr. after administration of the drugs. Glycogen accumulates preferentially in the right lobe. Subcutaneously injected tolbutamide has the same effect. Both sulphonylureas cause inhibition of glucose-6-phosphatase activity of rat liver homogenates in vitro, but at drug concentrations comparable with those found in plasma of treated patients the degree of inhibition is less than 10%. Livers from treated rats show normal glucose-6-phosphatase activity. The glucose uptake of the isolated rat diaphragm is unaffected by the sulphonylureas added in vitro. Diaphragms from treated rats show normal glucose uptake in the presence or absence of insulin. The inferences to be drawn from these results are discussed in the light of previous work. It is concluded that the sulphonylureas exert hypoglycaemic action by inhibiting glycogenolysis and it is suggested that they might do so by inhibiting release of glucagon from the pancreas.
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PMID:The action of hypoglycaemic sulphonylureas on carbohydrate metabolism in the fasted rat. 1346 Feb 43

The present study examines the effects of a hypercaloric diet on hepatic glucose metabolism of young rats, with and without monosodium glutamate (MSG) administration, and the association of these treatments with evaluating markers of oxidative stress. Male weaned Wistar rats (21 days old) from mothers fed with a hypercaloric diet or a normal diet, were divided into four groups (n=6): control (C) fed with control diet; (MSG) treated with MSG (4 mg/g) and control diet; (HD) fed with hypercaloric diet and (MSG-HD) treated with MSG and HD. Rats were sacrificed after the oral glucose tolerance test (OGTT), at 45 days of treatments. Serum was used for insulin determination. Glycogen, hexokinase(HK), glucose-6-phosphatase(G6PH), lipid hydroperoxide, superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) were determined in liver. HD rats showed hypoglycemia, hyperinsulinemia, and high hepatic glycogen, HK and decreased G6PH. MSG and MSG-HD had hyperinsulinemia, hyperglycemia, decreased HK and increased G6PH in hepatic tissue. These animals had impaired OGTT. HD, MSG and MSG-HD groups had increased lipid hydroperoxide and decreased SOD in hepatic tissue. Hypercaloric diet and monosodium glutamate administration induced alterations in metabolic rate of glucose utilization and decreased antioxidant defenses. Therefore, the hepatic glucose metabolic shifting induced by HD intake and MSG administration were associated with oxidative stress in hepatic tissue.
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PMID:Toxicity of hypercaloric diet and monosodium glutamate: oxidative stress and metabolic shifting in hepatic tissue. 1466 76


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