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Ann Burchell - One of the best experts on this subject based on the ideXlab platform.

  • Development of the rat hepatic microsomal Glucose-6-Phosphatase system and its glucocorticoid inducibility.
    Neonatology, 2009
    Co-Authors: Ann Burchell, Julian E.a. Leakey
    Abstract:

    Rat liver Glucose-6-Phosphatase activity was determined in both fully activated and intact microsomal preparations during perinatal development. Activities increased rapidly in both preparations following birth, then gradually fell to adult values. The latency of the Glucose-6-Phosphatase system also increased neonatally whereas hepatic glycogen concentrations decreased postnatally. The effect of dexamethasone pretreatment on the hepatic Glucose-6-Phosphatase system was also investigated. Dexamethasone pretreatment failed to decrease the latency of Glucose-6-Phosphatase in microsomes from neonatal rats but decreased the latency of the enzyme in adult female rat liver from 44 to 12% of total activity.

  • identification and characterisation of a new human Glucose 6 Phosphatase isoform
    FEBS Letters, 2003
    Co-Authors: Olivier Guionie, Eric Clottes, Kirsten Stafford, Ann Burchell
    Abstract:

    Abstract The liver endoplasmic reticulum Glucose-6-Phosphatase catalytic subunit (G6PC1) catalyses Glucose 6-phosphate hydrolysis during gluconeogenesis and glycogenolysis. The highest Glucose-6-Phosphatase activities are found in the liver and the kidney; there have been many reports of Glucose 6-phosphate hydrolysis in other tissues. We cloned a new G6Pase isoform (G6PC3) from human brain encoded by a six-exon gene (chromosome 17q21). G6PC3 protein was able to hydrolyse Glucose 6-phosphate in transfected Chinese hamster ovary cells. The optimal pH for Glucose 6-phosphate hydrolysis was lower and the Km higher relative to G6PC1. G6PC3 preferentially hydrolyzed other substrates including pNPP and 2-deoxy-Glucose-6-phosphate compared to the liver enzyme.

  • Histone 2A stimulates Glucose-6-Phosphatase activity by permeabilization of liver microsomes.
    Biochemical Journal, 2002
    Co-Authors: Angelo Benedetti, Rosella Fulceri, Paola Marcolongo, Brian Burchell, Bernard B. Allan, Pamela Houston, Andrey Sukhodub, Brian T. Ethell, Ann Burchell
    Abstract:

    Histone 2A increases Glucose-6-Phosphatase activity in liver microsomes. The effect has been attributed either to the conformational change of the enzyme, or to the permeabilization of microsomal membrane that allows the free access of substrate to the intraluminal Glucose-6-Phosphatase catalytic site. The aim of the present study was the critical reinvestigation of the mechanism of action of histone 2A. It has been found that the dose-effect curve of histone 2A is different from that of detergents and resembles that of the pore-forming alamethicin. Inhibitory effects of EGTA on Glucose-6-Phosphatase activity previously reported in histone 2A-treated microsomes have been also found in alamethicin-permeabilized vesicles. The effect of EGTA cannot therefore simply be an antagonization of the effect of histone 2A. Histone 2A stimulates the activity of another latent microsomal enzyme, UDP-glucuronosyltransferase, which has an intraluminal catalytic site. Finally, histone 2A renders microsomal vesicles permeable to non-permeant compounds. Taken together, the results demonstrate that histone 2A stimulates Glucose-6-Phosphatase activity by permeabilizing the microsomal membrane.

  • Therapeutic insulin and hepatic Glucose-6-Phosphatase activity in preterm infants.
    Archives of Disease in Childhood-fetal and Neonatal Edition, 2000
    Co-Authors: Ann Burchell, A. Mcgeechan, R Hume
    Abstract:

    BACKGROUND Hepatic Glucose-6-Phosphatase activity is low at birth, and in term infants rises rapidly to adult levels. In contrast, in most preterm infants, it remains low postnatally making them vulnerable to repeated hypoglycaemic episodes, resultant cerebral damage, or risk of sudden and unexpected death. AIMS To investigate the clinical features of preterm infants with low Glucose-6-Phosphatase enzyme activity to determine the influencing factors. METHODS Clinical data from 36 preterm infants were correlated by stepwise multiple regression analysis with V max of hepatic Glucose-6-Phosphatase as the dependent variable. RESULTS The most significant correlation was with the administration of insulin (units/kg/h postnatal life) with lesser effects of respiratory distress syndrome and dopamine administration. The V max changes reflected changes in the level of expression of the Glucose-6-Phosphatase protein. CONCLUSION In a variety of animal models, hepatic Glucose-6-Phosphatase levels have been shown to decrease in response to insulin, which also decreases transcription of the Glucose-6-Phosphatase gene. The association of insulin administration with high levels of hepatic Glucose-6-Phosphatase activity and protein expression was therefore most unexpected. Results from model systems, or adults, must be extrapolated to the metabolism of preterm infants with caution.

  • Glucose induces Glucose 6 Phosphatase hydrolytic subunit gene transcription in an insulinoma cell line ins 1
    FEBS Letters, 1999
    Co-Authors: Dieter Schmoll, Sharlene L Watkins, Christina Wasner, Reinhard Walther, Ann Burchell
    Abstract:

    Primer extension analysis and RNase protection assays revealed the identity of Glucose 6-Phosphatase gene transcripts in both the insulinoma cell line INS-1 and hepatic cells. In transient transfection assays of INS-1 cells, using constructs between the human Glucose 6-Phosphatase gene promoter and a luciferase reporter gene, the reporter gene activity was induced by dexamethasone and dibutyryl cAMP. Furthermore, the promoter was regulated by the Glucose concentration in the medium. This effect was dependent on Glucose metabolism. The data indicated that Glucose 6-Phosphatase gene transcription is regulated in a similar way in the insulinoma cell line and in liver.

Janice Yang Chou - One of the best experts on this subject based on the ideXlab platform.

  • isolation of the gene for murine Glucose 6 Phosphatase the enzyme deficient in glycogen storage disease type 1a
    Journal of Biological Chemistry, 1993
    Co-Authors: L L Shelly, Kejian Lei, Chijiunn Pan, S F Sakata, S Ruppert, Gunther Schutz, Janice Yang Chou
    Abstract:

    Abstract Glycogen storage disease (GSD) type 1a (von Gierke disease) is caused by a deficiency in Glucose-6-Phosphatase, the key enzyme in Glucose homeostasis catalyzing the terminal step in gluconeogenesis and glycogenolysis. Despite its clinical importance, this membrane-bound enzyme has eluded molecular characterization. Here we report the cloning and characterization of a murine Glucose-6-Phosphatase cDNA by screening a mouse liver cDNA library differentially with mRNA populations representing the normal and the albino deletion mouse known to express markedly reduced Glucose-6-Phosphatase activity. Additionally, we identified the gene that consists of 5 exons. Biochemical analyses indicate that the in vitro expressed enzyme is indistinguishable from mouse liver microsomal Glucose-6-Phosphatase exhibiting essentially identical kinetic constants, latency, thermal lability, and vanadate sensitivity. The characterization of the murine Glucose-6-Phosphatase gene opens the way for studying the molecular basis of GSD type 1a in humans and its etiology in an animal model.

A Burchell - One of the best experts on this subject based on the ideXlab platform.

  • Abnormal expression of Glucose-6-Phosphatase in preterm infants.
    Archives of Disease in Childhood, 1993
    Co-Authors: R Hume, A Burchell
    Abstract:

    The hepatic microsomal Glucose-6-Phosphatase enzyme was studied in liver samples from 76 premature infants including 15 victims of sudden infant death syndrome. The data obtained were compared with Glucose-6-Phosphatase activity in liver samples from 95 term infants. In the majority of preterm infants up to 350 days of age the activity of the Glucose-6-Phosphatase enzyme was at or below the extreme low limit of the normal range in term infants. The premature infants with the lowest hepatic microsomal Glucose-6-Phosphatase activities are likely to be at risk of hypoglycaemic episodes during periods of relative starvation or stress.

  • Impairment of the activity of the hepatic microsomal Glucose‐6‐Phosphatase system in three preterm infants
    Acta Paediatrica, 1992
    Co-Authors: Robert Hume, M Giles, Helen Lyall, A Burchell
    Abstract:

    Three preterm infants born at 26–30 weeks' gestation who died between 103 and 266 days after birth were found to have elevated hepatic glycogen levels. Kinetic analysis of the hepatic microsomal Glucose-6-Phosphatase system demonstrated that one infant had abnormally low levels of activity of the Glucose-6-Phosphatase enzyme (partial type 1 a glycogen storage disease) and two had deficiencies of T2, a microsomal phosphate/pyrophosphate transport protein (type lc glycogen storage disease). In all three cases glycogen storage disease was not suspected prior to death even though both hypo- and hyperglycaemic episodes were recorded in the first 15 days after birth indicating that they had somewhat disordered blood Glucose regulation. In the infant with low Glucose-6-Phosphatase enzyme activity, abnormal development of the Glucose-6-Phosphatase enzyme cannot be ruled out. This is the first description of abnormalities in the Glucose-6-Phosphatase system in preterm infants.

  • Characterization of Glucose-6-Phosphatase in hepatocytes. Effects of amiloride and pentamidine.
    Biochemical pharmacology, 1991
    Co-Authors: A Grant, A M Macgregor, A Burchell
    Abstract:

    The hepatic microsomal Glucose-6-Phosphatase enzyme is situated inside the lumen of the endoplasmic reticulum and, for normal enzyme activity in vivo, three transport systems are needed for the substrate Glucose-6-phosphate and the products phosphate and Glucose. Previous studies using isolated microsomes showed that the drugs amiloride and pentamidine do not affect the Glucose-6-Phosphatase enzyme but can activate the Glucose-6-phosphate transport system. Here we demonstrate that, very surprisingly, the addition of pentamidine (and to a lesser extent amiloride) to isolated hepatocytes results in an inhibition of the catalytic subunit of Glucose-6-Phosphatase.

  • Transverse topology of Glucose-6-Phosphatase in rat hepatic endoplasmic reticulum.
    The Biochemical journal, 1991
    Co-Authors: I D Waddell, A Burchell
    Abstract:

    Antibodies raised against purified components of Glucose-6-Phosphatase were used to study the transmembrane orientation of the complex. Measurements of Glucose-6-Phosphatase activities and immunoblot analysis of sealed microsomes and detergent-solubilized microsomes after treatment with proteases suggested that most of the catalytic subunit resides within the lumen of the endoplasmic reticulum. In contrast, other components of Glucose-6-Phosphatase are accessible to the cytoplasm. Treatment of the partially purified Glucose-6-Phosphatase enzyme with glycopeptide N-glycosidase indicated that the catalytic subunit of the enzyme was a glycoprotein.

Tarik Issad - One of the best experts on this subject based on the ideXlab platform.

  • o glycosylation of foxo1 increases its transcriptional activity towards the Glucose 6 Phosphatase gene
    FEBS Letters, 2008
    Co-Authors: Meishiue Kuo, Vladimir Zilberfarb, Nicolas Gangneux, Nevena Christeff, Tarik Issad
    Abstract:

    Mono-O-glycosylations post-translationally regulate the activity of nucleocytoplasmic proteins. We showed that glucosamine and an inhibitor of deglycosylation (PUGNAc) induced O-glycosylation of FoxO1, resulting in increased expression of a Glucose-6-Phosphatase reporter gene. This effect was independent of FoxO1 re-localisation, since it was also observed with constitutively nuclear FoxO1-AAA mutant. Moreover, in HepG2 cells, glucosamine and PUGNAc have a synergistic effect on the Glucose-6-Phosphatase reporter gene, and this effect was inhibited by FoxO1 siRNAs. Since Glucose-6-Phosphatase plays a key role in hepatic Glucose production, our observation may be of importance with regard to glucotoxicity associated with chronic hyperglycaemia in diabetes.

Sharlene L Watkins - One of the best experts on this subject based on the ideXlab platform.

  • Glucose induces Glucose 6 Phosphatase hydrolytic subunit gene transcription in an insulinoma cell line ins 1
    FEBS Letters, 1999
    Co-Authors: Dieter Schmoll, Sharlene L Watkins, Christina Wasner, Reinhard Walther, Ann Burchell
    Abstract:

    Primer extension analysis and RNase protection assays revealed the identity of Glucose 6-Phosphatase gene transcripts in both the insulinoma cell line INS-1 and hepatic cells. In transient transfection assays of INS-1 cells, using constructs between the human Glucose 6-Phosphatase gene promoter and a luciferase reporter gene, the reporter gene activity was induced by dexamethasone and dibutyryl cAMP. Furthermore, the promoter was regulated by the Glucose concentration in the medium. This effect was dependent on Glucose metabolism. The data indicated that Glucose 6-Phosphatase gene transcription is regulated in a similar way in the insulinoma cell line and in liver.

  • Human fetal testis endoplasmic reticulum Glucose-6-Phosphatase enzyme protein.
    Biology of Reproduction, 1996
    Co-Authors: Ann Burchell, Sharlene L Watkins, Robert Hume
    Abstract:

    Microsomal Glucose-6-Phosphatase (EC 3.1.3.9) is an enzyme system traditionally thought to be present only in gluconeogenic tissues. We have used microassay techniques, immunohistochemistry using monospecific antibodies to the liver enzyme, and specific DNA probes and primers to examine whether Glucose-6-Phosphatase is present in human and rat testis. Microsomal Glucose-6-Phosphatase activities in human fetal testis (weeks 15-20 of gestation) are approximately 25% of corresponding liver values. Localization is predominantly in Leydig cells, with variable and weak immunoreactivity in developing seminiferous tubules. Kinetic analysis of Glucose-6-Phosphatase in intact and disrupted microsomes and Southern blot analysis of polymerase chain reaction products indicated that the specific Glucose-6-Phosphatase enzyme system was also present in rat testis. We have shown for the first time that specific microsomal Glucose-6-Phosphatase activity, protein, and mRNA are present in testis, and that the predominant site of expression is the Leydig cell in human fetal testis.

  • A Comparison of the Renal and Hepatic Microsomal Glucose-6-Phosphatase Enzymes
    Archives of Biochemistry and Biophysics, 1996
    Co-Authors: Michael W. Voice, Sharlene L Watkins, Hazel M. Scott, Claire Middleditch, Ann Burchell
    Abstract:

    The liver Glucose-6-Phosphatase enzyme has been extensively characterized and relatively little is known about the renal microsomal Glucose-6-Phosphatase enzyme. The reason for lack of study of the renal Glucose-6-Phosphatase enzyme is that it has been assumed to be the same as the liver enzyme. Immunoblotting with antibodies raised against the liver enzyme revealed differences in apparent molecular weight and antigenicity between the liver and kidney Glucose-6-Phosphatase enzyme proteins. Characterization of the activity of the renal Glucose-6-Phosphatase enzyme also showed that it is regulated differently to the liver enzyme in some metabolic states. This implies that the renal and liver Glucose-6-Phosphatase enzymes may have different roles.