A Burchell

University of Dundee, Dundee, Scotland, United Kingdom

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Publications (172)748.14 Total impact

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    ABSTRACT: G6PC3 is a widely expressed isoform of glucose-6-phosphatase, found in many foetal and adult tissues. Mutations in this gene cause developmental abnormalities and severe neutropenia due to abolition of glucose recycling between the cytoplasm and endoplasmic reticulum. Low G6PC3 expression as a result of promoter polymorphisms or dysregulation could produce similar outcomes. Here we investigated the regulation of human G6PC3 promoter activity. HeLa and H4IIE cells were transiently transfected with G6PC3 promoter coupled to the firefly luciferase gene, and promoter activity was measured by dual luciferase assay. Activity was highest in a 453 bp segment of the G6PC3 promoter, from -455 to -3 relative to the transcriptional start site. This promoter was unresponsive to glucostatic hormones. Its activity increased significantly between 1 and 5.5 mM glucose, and was not elevated further by glucose concentrations up to 25 mM. Pyruvate increased its activity, but β-hydroxybutyrate and sodium acetate did not. Promoter activity was reduced by inhibitors of hexokinase, glyceraldehyde phosphate dehydrogenase and the oxidative branch of the pentose phosphate pathway, but not by a transketolase inhibitor. Deletion of two adjacent Enhancer-boxes (-274 to -279 and -299 to -304) reduced promoter activity and abolished the glucose effect, suggesting they could function as a glucose response element. Deletion of an additional downstream 140 bp (-140 to -306) restored activity, but not the glucose response, suggesting the presence of repressor elements in this region. 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) reduced promoter activity, showing dependence on AMP-kinase. Regulation of the G6PC3 promoter is thus radically different to that of the hepatic isoform, G6PC. It is sensitive to carbohydrate, but not to fatty acid metabolites, and at much lower physiological concentrations. Based on these findings, we speculate that reduced G6PC3 expression could occur during hypoglycemic episodes in vivo, which are common in utero and in the postnatal period. If such episodes lower G6PC3 expression they could place the foetus or infant at risk of impaired immune function and development, and this possibility requires further examination both in vitro and in vivo.
    Molecular Genetics and Metabolism 07/2011; 103(3):254-61. · 2.83 Impact Factor
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    ABSTRACT: Background Human placenta may be capable of glucose release due to the presence of Glucose-6-Phosphatase (G6Pase). This release may be from placental glycogen. The authors hypothesised that there would be differences in G6Pase activity and glycogen content in normal pregnancy and small for gestational age (SGA) pregnancies.Methods48 subjects were recruited to the Appropriate for gestational Age (AGA) group and 48 subjects to the SGA group. SGA was defined as an ultrasound measurement of abdominal circumference 95th centile) and Group 2 (N=19) with Normal Doppler (ND). The placentas were collected postdelivery and analysed for G6Pase activity and glycogen content.ResultsThere was no significant difference in G6Pase activity in the AGA group and SGA group (9.42±2.79 vs 9.1±2.68) mg/min, (p=0.675) and between the SGA ND and SG AD (8.9±2.66 vs 9.6±2.7) mg/min, (p=0.435). Glycogen content in the AGA group was significantly lower compared to the SGA group (3.87 (2.89–5.35) vs 6.2 (4.4–10.35), p=0.001) per mg protein but no significant difference in the glycogen content in SGA ND compared to SGA AD (p=0.242).ConclusionG6Pase activity is similar in AGA and SGA pregnancies. SGA placentas contain more glycogen than AGA subjects which is not explained by G6Pase activity. SGA ND and AD pregnancies display no differences in G6Pase activity and glycogen content.
    Archives of Disease in Childhood-fetal and Neonatal Edition - ARCH DIS CHILD-FETAL NEONATAL. 01/2010; 95(1).
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    ABSTRACT: Genetic deficiencies of the hepatic glucose-6-phosphatase system, either of the enzyme (G6PC1) or of the glucose-6-phosphate transporter (G6PT1), result in fasting hypoglycaemia. Low hepatic G6PC1 activities were previously reported in a few term sudden infant death syndrome (SIDS) infants and assumed to be due to G6PC1 genetic deficiencies. In preterm infants, failures of postnatal activation of G6PC1 expression suggest disordered development as a novel cause of decreased G6PC1 activity in SIDS. G6PC1 and G6PT1 functional and mutational analysis was investigated in SIDS and non-SIDS infants. G6PC1 hepatic activity was abnormally low in 98 SIDS (preterm, n=13; term, n=85), and non-SIDS preterm infants (n=35) compared to term non-SIDS infants (n=29) and adults (n=9). Mean glycogen levels were elevated, except in term non-SIDS infants. A novel G6PT1 promoter polymorphism, 259C --> T was found; the - 259*T allele frequency was greater in term SIDS infants (n=140) than in term control infants (n=119) and preterm SIDS infants (n=30). Heterozygous and homozygous prevalence of 259C --> T was 38.6% and 7.1%, respectively, in term SIDS infants. In cell-based expression systems, the presence of - 259T in the promoter decreased basal luciferase activity by 3.2-fold compared to - 259C. Glucose-6-phosphatase latency in hepatic microsomes was elevated (indicating decreased G6PT1 function) in heterozygous and homozygous - 259T states. Delayed postnatal appearance of hepatic glucose-6-phosphatase in infants makes them vulnerable to hypoglycaemic episodes and this may occur in some SIDS infants. However, SIDS may be an association of more complex phenotypes in which several genes interact with multiple environmental factors. A UK-wide DNA Biobank of samples from all infant deaths, with an accompanying epidemiological database, should be established by pathologists to allow cumulative data to be collected from multiple genetic investigations on the same large cohort of samples, with the aim of selection of the best combination of genetic markers to predict unexpected infant death.
    The Journal of Pathology 05/2007; 212(1):112-20. · 7.59 Impact Factor
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    ABSTRACT: Glucose transfer from mother to fetus by placental facilitated diffusion is the dominant mechanism by which the fetus acquires glucose. In small for gestational age pregnancies, fetal glucose concentrations tend to be lower than normal and this persists following delivery. GLUT1 is the major glucose transporter in human placenta but there is no evidence of GLUT1 deficiency as a cause of the lower fetal glucose concentration in small for gestational age pregnancy. The physiological and pathological roles of the other glucose transporters (and there are 14 currently described) are unknown. In recent years, the possibility has been raised that the placenta is itself capable of supplying glucose for fetal needs. This hypothesis derived from glucose isotope studies in normal pregnancy, where dilution of glucose isotope was demonstrated in blood samples taken from the fetal circulation during intravenous infusion of glucose isotope in the mother. Although other gluconeogenic enzymes were known to be present, the placenta was previously considered incapable of glucose secretion because it lacked functional glucose-6-phosphatase. Recent studies, however, have suggested that specific glucose-6-phosphatase may be present in placenta but it may be the product of a different gene from conventional hepatic glucose-6-phosphatase. The presence of the specific transporters necessary for glucose-6-phosphatase activity is currently being investigated. The role of placental glucose secretion in normal and growth-restricted pregnancies is an area of current study.
    Placenta 05/2006; 27 Suppl A:S103-8. · 3.12 Impact Factor
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    ABSTRACT: Sudden and unexpected infant deaths can be unexplained [sudden infant death syndrome (SIDS)] or explained (non-SIDS) but risk factors including lower birthweight are similar in both groups. Mutations in the glucokinase (GK) gene result in Maturity Onset Diabetes of the Young type 2 (MODY 2) and are associated with lower birthweight. Low hepatic glucose-6-phosphatase (G6PC1) expression occurs in both low birthweight and SIDS infants. We investigated whether polymorphisms are prevalent in the GK and G6PC1 genes in infants who died suddenly and unexpectedly. Mutation analysis was performed by polymerase chain reaction (PCR) and denaturing high-performance liquid chromatography (DHPLC) in samples from 126 infants who died suddenly and unexpectedly (78 SIDS, 48 non-SIDS) and from 70 healthy, living infants. G6PC1 promoter polymorphism significance was investigated by transfection of reporter gene constructs into a H4IIE cell line. Heterozygous GK polymorphisms were identified in 17.9% of SIDS and 20.8% of non-SIDS infants: two rare silent polymorphisms, Y215Y and S263S, in the coding region; a third rare polymorphism, -45G>A, in the hepatic promoter and the most prevalent polymorphism, c.484-29G>C, in a non-coding region upstream from the intron 4-exon 5 junction. A novel heterozygous polymorphism -77G>A in the G6PC1 promoter in 6.3% of non-SIDS and 2.9% of control infants decreased basal G6PC1 promoter activity (p<0.001). We describe three novel polymorphisms in the GK gene, S263S, -45G>A, and a common (14.3%) intronic substitution, c.484-29G>C, in infants who died suddenly and unexpectedly. We identified the first G6PC1 promoter polymorphism, which lowers expression, potentially increasing risk of hypoglycaemia and hence risk of sudden and unexpected death.
    Journal of Molecular Medicine 09/2005; 83(8):610-8. · 4.77 Impact Factor
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    ABSTRACT: Glucose 6-phosphate transport has been well characterized in liver microsomes. The transport is required for the functioning of the glucose-6-phosphatase enzyme that is situated in the lumen of the hepatic endoplasmic reticulum. The genetic deficiency of the glucose 6-phosphate transport activity causes a severe metabolic disease termed type 1b glycogen storage disease. The cDNA encoding a liver transporter for glucose 6-phosphate was cloned and was found to be mutated in patients suffering from glycogen storage disease 1b. While related mRNAs have been described in liver and other tissues, the encoded protein(s) has not been immunologically characterized yet. In the present study, we report (using antibodies against three different peptides of the predicted amino acid sequence) that a major protein encoded by the glucose 6-phosphate transporter gene is expressed in the endoplasmic reticulum membranes of rat and human liver. The protein has an apparent molecular mass of approx. 33 kDa using SDS/PAGE, but several lines of evidence indicate that its real molecular mass is 46 kDa, as expected. The glucose 6-phosphate transporter protein was also immunodetected in kidney microsomes, but not in microsomes derived from human fibrocytes, rat spleen and lung, and a variety of cell lines. Moreover, little or no expression of the glucose 6-phosphate transporter protein was found in liver microsomes obtained from three glycogen storage disease 1b patients, even bearing mutations that do not directly interfere with protein translation, which can be explained by a (proteasome-mediated) degradation of the mutated transporter.
    Biochemical Journal 08/2005; 389(Pt 1):57-62. · 4.65 Impact Factor
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    ABSTRACT: Hepatic glucose production by glycogenolysis and gluconeogenesis is essential to maintain blood glucose levels, and the glucose-6-phosphatase system catalyses the terminal step of both pathways. Developmental delays in the postnatal up-regulation of hepatic glucose-6-phosphatase enzyme activity are common in preterm infants. Two groups of infants have been identified with failure of developmental regulation of glucose homeostasis. Firstly, up to 20% of preterm infants about to be discharged home are at risk of hypoglycaemia if a feed is delayed. Cortisol, corticotrophin and epinephrine levels are higher in the infants with severe and persistent hypoglycaemia, but insulin, glucagon and human growth hormone do not differ from normoglycaemic infants. Secondly, preterm infants with an inadequate glycaemic response to glucagon (30% at the time of discharge home) have relative fasting hyperglycaemia, hyperinsulinaemia, increased insulin:glucagon ratios and a lower insulin sensitivity index. Hormonal dysfunctions in preterm infants may contribute to failures in postnatal expression of hepatic enzymes.
    Early Human Development 02/2005; 81(1):95-101. · 2.02 Impact Factor
  • Andrey L Sukhodub, Ann Burchell
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    ABSTRACT: Mammalian cell culture is widely used for the cloning and expression of insoluble proteins. The established methods of sub-cellular fractionation of tissues are not always directly suitable for the sub-cellular fractionation of cultured cells. In this study we have optimized the conditions for the preparation of microsomal fractions from cultured cells with the aim of isolating intact vesicles that are suitable for the assay of transport proteins and lumenal enzymes. H4IIE cell cultures were used as a convenient model with high latency of internal endoplasmic reticulum enzyme glucose-6-phosphatase towards mannose-6-phosphate. Also 7-ethoxyresorufin O-deethylase (EROD) activity was determined as a reflection of the state of monooxygenase system. The variations in a number of homogenization strokes and buffer composition revealed that one homogenization stroke in glass homogenizer with 0.25 M sucrose, 5 mM HEPES, pH 7.4 buffer provides the best latency/activity ratio for homogenates, but for the isolation of microsomes the higher number of strokes (10) as well as low-osmotic buffer (5 mM HEPES, pH 7.4) are needed. However EROD activity is largely reduced in the preparations using buffers containing sucrose, so 5 mM HEPES buffer is recommended as the most suitable to study the microsomal reactions in H4IIE cells. The isolation of microsomes was followed by the significant proteolytic breakdown of the glucose-6-phosphatase enzyme. It is recommended to use cell culture homogenates for assays when possible.
    Journal of Pharmacological and Toxicological Methods 01/2005; 52(3):330-4. · 2.15 Impact Factor
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    ABSTRACT: The purpose of this study was to define plasma catecholamine responses as part of the counterregulatory hormonal reaction to hypoglycemia in infants after a regular 3- to 4-h feed was omitted. Hormone levels were assessed once, at the end of the fast or at hypoglycemia. The 121 infants were subdivided into three groups for analysis: normoglycemia (n = 94, 78%); transient hypoglycemia (n = 11, 9%); or severe and persistent hypoglycemia (n = 16, 13%). The severe and persistent hypoglycemic group had significantly higher levels of cortisol and epinephrine than the normoglycemic group. Norepinephrine and glucagon levels did not differ between the groups. Human GH levels were higher in the transiently hypoglycemic group but not in the severe and persistent hypoglycemic group. Prefeed blood lactate levels differed significantly among the groups and were highest in the severe and persistent groups. Multiple regression analysis showed that cortisol levels were significantly higher in infants who had severe and persistent hypoglycemia. The counterregulatory hormonal response in infants to severe and persistent hypoglycemia was limited to elevations in only cortisol and epinephrine levels but did not involve glucagon or human GH. This limited hormonal response may also contribute to the frequent occurrence of hypoglycemia in these infants.
    Journal of Clinical Endocrinology &amp Metabolism 01/2005; 89(12):6251-6. · 6.43 Impact Factor
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    ABSTRACT: Glucocorticoid and thyroid hormones (T3) are important for the development of the lungs' Na+ absorbing phenotype, which is essential for the integrated functioning of the respiratory tract. Electrometric studies of H441 airway epithelial cells confirmed that dexamethasone increases apical Na+ conductance (GNa) and demonstrated that T3 facilitates this control over GNa. Assays of transcriptional activity showed that dexamethasone caused concentration-dependent activation of the human alpha-ENaC promoter (EC50 approximately 5 nM) but, despite its clear effect on GNa, T2 had no effect upon the transcriptional response to dexamethasone. The facilitation of Na+ transport may thus reflect control over events downstream to transcription.
    FEBS Letters 11/2004; 576(3):339-42. · 3.58 Impact Factor
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    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 K(m) higher relative to G6PC1. G6PC3 preferentially hydrolyzed other substrates including pNPP and 2-deoxy-glucose-6-phosphate compared to the liver enzyme.
    FEBS Letters 10/2003; 551(1-3):159-64. · 3.58 Impact Factor
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    ABSTRACT: Glucose-6-phosphatase is a multicomponent system located in the endoplasmic reticulum, involving both a catalytic subunit (G6PC) and several substrate and product carriers. The glucose-6-phosphate carrier is called G6PT1. Using light scattering, we determined K(D) values for phosphate and glucose transport in rat liver microsomes (45 and 33mM, respectively), G6PT1 K(D) being too low to be estimated by this technique. We provide evidence that phosphate transport may be carried out by an allosteric multisubunit translocase or by two distinct proteins. Using chemical modifications by sulfhydryl reagents with different solubility properties, we conclude that in G6PT1, one thiol group important for activity is facing the cytosol and could be Cys(121) or Cys(362). Moreover, a different glucose-6-phosphate translocase, representing 20% of total glucose-6-phosphate transport and insensitive to N-ethylmaleimide modification, could coexist with liver G6PT1. In the G6PC protein, an accessible thiol group is facing the cytosol and, according to structural predictions, could be Cys(284).
    Archives of Biochemistry and Biophysics 01/2003; 408(1):33-41. · 3.37 Impact Factor
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    L Jackson, A Burchell, A McGeechan, R Hume
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    ABSTRACT: To define clinical, metabolic, and hormonal characteristics of preterm infants relative to glucagon responsiveness. Two phase study of 78 preterm infants (25-36 weeks gestation) on regular four hourly feeds anticipating discharge home at 36 weeks mean corrected gestation. In phase 1 infants were fasted until hypoglycaemic, or maximally for eight hours. Endocrine and metabolic profiles were obtained at completion. Phase 2 was performed the following day. A feed was omitted and replaced by a bolus dose of intravenous glucagon (100 micro g/kg). Main outcome measures were measurements of blood glucose and lactate concentrations, taken immediately pre-glucagon, and thereafter every 15 minutes for 60 minutes. A rise in glucose concentration of >1 mmol/l (55 infants) was defined as an adequate response to glucagon. An inadequate glycaemic response was <1 mmol/l (23 infants). Several differences in fasting blood glucose and hormone concentrations were identified in infants with an inadequate glycaemic response to glucagon compared to those with an adequate response: relative fasting hyperglycaemia (mean 3.7 v 3.3 mmol/l, p = 0.008); fasting hyperinsulinaemia (mean 4.3 v 2.6 mU/l, p = 0.014); an increased insulin:glucagon ratio (0.19 v 0.11, p = 0.014), and a lower insulin sensitivity QUICKI index (0.19 v 0.22, p = 0.04). There was no distinctive phenotype to reliably predict response to glucagon. Some preterm infants show an inadequate glycaemic response to glucagon and have features suggestive of insulin resistance. The potential long term implications of such insulin resistance may have appreciable public health consequences.
    Archives of Disease in Childhood - Fetal and Neonatal Edition 01/2003; 88(1):F62-6. · 3.45 Impact Factor
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    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.
    Biochemical Journal 11/2002; 367(Pt 2):505-10. · 4.65 Impact Factor
  • A Burchell, L Forsyth, R Hume
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    ABSTRACT: Infants with intra-uterine growth retardation have an increased risk of Sudden Infant Death Syndrome (SIDS). Hypoglycaemia is also significantly correlated with retardation of intra-uterine growth. A number of mutations in key proteins involved in regulation of blood glucose (e.g. glucokinase) have been found to result in reduced birth weight. Heterozygous mutations in the coding region of the glucokinase gene have been shown to cause MODY (a form of early onset Type II diabetes mellitus). The aim was to screen a cohort of SIDS and control infants who were either growth retarded or appropriately grown for gestational age to determine if any mutations and/or polymorphisms were present in the glucokinase gene. PCR, denaturing high performance liquid chromatography on an automated Transgenomic WAVE DNA fragment analysis system and DNA sequencing. Genomic DNA was isolated from 129 infants who were either growth retarded or appropriately grown for gestational age. We found several rare novel polymorphisms in the glucokinase gene in the infant samples. However, none of the samples contained any of the mutations in the glucokinase gene previously reported in cases of MODY. We have found rare novel polymorphisms in the glucokinase gene in the infant samples. In contrast in these samples, we have not found any examples of the previously reported mutations in the coding region of the glucokinase gene found in MODY. This clearly shows that while MODY babies are often small, MODY is not a common cause of either intra-uterine growth retardation or of SIDS.
    Child Care Health and Development 10/2002; 28 Suppl 1:37-9. · 1.70 Impact Factor
  • R Hume, A McGeechan, A Burchell
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    ABSTRACT: Developmental failures to adequately control postnatal blood glucose levels are common in the transition from fetal to infant life and can persist for many months. The standard method of functionally measuring hepatic glucose production and/or disordered glucose production is the response to a glucagon tolerance test. We adapted the standard glucagon tolerance test used for children and adults for use in preterm infants. 79 consecutive preterm infants gestational age range 25-36 weeks (mean 32.2 weeks), mean birth weight 1.66 kg admitted to the Neonatal Intensive Care Unit, Ninewells Hospital, Dundee and who survived to discharge home were recruited into the study. At the time of discharge home the characteristics of the group were as follows: adjusted mean gestational age 36.7 weeks, mean discharge weight 2.23 kg. In this study of preterm infants the maximal increase in plasma glucose following administration of a glucagon tolerance test is 1.39 +/- 07 mmol/L, n = 78 (range 0-3.98 mmol/L). An increase in plasma glucose of less than 4 mmol/L is considered abnormal in adults following administration of a fasting glucagon tolerance test. The responses of preterm infants and adults to glucagon are clearly different. The attenuated response to glucagon in the preterm infants is consistent with the low levels of hepatic glucose-6-phosphatase activity in premature infants as glucose-6-phosphatase is the terminal step of the two main pathways of liver glucose production.
    Child Care Health and Development 10/2002; 28 Suppl 1:45-7. · 1.70 Impact Factor
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    ABSTRACT: Excessive glucose production by the liver contributes significantly to diabetic hyperglycemia. The enzyme system glucose-6-phosphatase plays a key role in regulating hepatic glucose production and therefore its inhibition is a potential therapeutic target for the correction of hyperglycemia. It has previously been shown that sulfated steroids, such as estrone sulfate and dehydroepiandrosterone sulfate, inhibit the glucose-6-phosphatase system in vitro, principally through inhibition of endoplasmic reticulum glucose-6-phosphate transport. We report here that in the obese/diabetic ob/ob mouse model, orally administered estrone sulfate reduces the abnormally elevated hepatic glucose-6-phosphatase enzyme activity and enzyme protein levels that are characteristic in the ob/ob mouse, and that this reduction is associated with normalization of blood glucose levels. Other sulfated and non-sulfated steroids also reduced, to a lesser extent, glucose-6-phosphatase enzyme activity - with the exception of dehydroepiandrosterone sulfate, which had no apparent effect on this system in ob/ob mice. Estrone sulfate is therefore an effective antihyperglycemic agent in ob/ob mice, and the glucose-6-phosphatase system can be successfully targeted for the therapeutic management of hyperglycemia in this animal model of non-insulin-dependent diabetes mellitus.
    Hormone and Metabolic Research 01/2002; 33(12):721-6. · 2.15 Impact Factor
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    ABSTRACT: In liver endoplasmic reticulum the intralumenal glucose-6-phosphatase activity requires the operation of a glucose 6-phosphate transporter (G6PT1). Mutations in the gene encoding G6PT1 cause glycogen storage disease type 1b, which is characterized by a loss of glucose-6-phosphatase activity and impaired glucose homoeostasis. We describe a novel glucose 6-phosphate (G6P) transport activity in microsomes from human fibroblasts and HeLa cells. This transport activity is unrelated to G6PT1 since: (i) it was similar in microsomes of skin fibroblasts from glycogen storage disease type 1b patients homozygous for mutations of the G6PT1 gene, and in microsomes from human control subjects; (ii) it was insensitive to the G6PT1 inhibitor chlorogenic acid; and (iii) it was equally active towards G6P and glucose 1-phosphate, whereas G6PT1 is highly selective for G6P. Taken together, our results provide evidence for the presence of multiple transporters for G6P (and other hexose phosphoesters) in the endoplasmic reticulum.
    Biochemical Journal 08/2001; 357(Pt 2):557-62. · 4.65 Impact Factor
  • Biochemical Journal 07/2001; 357(2):557. · 4.65 Impact Factor
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    ABSTRACT: The expression of two components of the glucose-6-phosphatase system, the catalytic subunit (G6PaseC) and the glucose-6-phosphate transporter, was analyzed in the clear cell type of human renal cell carcinoma. The expression of G6PaseC was decreased in tumours compared with non-tumourous tissue of the same patient. The expression of G6PaseT varied with no general trend between tumours and control tissue. The expression of protein kinase B (PKB) was unchanged in the tumours, suggesting that the down-regulation of G6PaseC in clear cells and the maintenance of the transformed phenotype are not predominantly caused by an overexpression of PKB.
    Cancer Letters 07/2001; 167(1):85-90. · 4.26 Impact Factor

Publication Stats

3k Citations
748.14 Total Impact Points


  • 1976–2011
    • University of Dundee
      • • School of Medicine
      • • Institute for Medical Science and Technology (IMSaT)
      Dundee, Scotland, United Kingdom
  • 1987–2006
    • Ninewells Hospital
      Dundee, Scotland, United Kingdom
  • 2005
    • University of Portsmouth
      • School of Biological Sciences
      Portsmouth, ENG, United Kingdom
  • 1992–2002
    • Università degli Studi di Siena
      • Department of Molecular & Developmental Medicine
      Siena, Tuscany, Italy
    • University of North Dakota
      • Department of Biochemistry and Molecular Biology
      Grand Forks, ND, United States
  • 1999
    • University of Greifswald
      • Division of Biochemistry
      Greifswald, Mecklenburg-Vorpommern, Germany
  • 1998
    • Rutgers, The State University of New Jersey
      • Department of Pharmacology and Toxicology
      New Brunswick, NJ, United States
  • 1996
    • Newcastle University
      Newcastle-on-Tyne, England, United Kingdom
  • 1995
    • The Royal Children's Hospital
      Melbourne, Victoria, Australia
  • 1993
    • The University of Edinburgh
      • Department of Child Life and Health
      Edinburgh, SCT, United Kingdom
  • 1991
    • Hadassah Medical Center
      Yerushalayim, Jerusalem District, Israel
  • 1989
    • University of Miami Miller School of Medicine
      • Division of Hospital Medicine
      Miami, FL, United States
  • 1982
    • Cornell University
      • Department of Nutritional Sciences
      Ithaca, NY, United States
  • 1978
    • University of Birmingham
      Birmingham, England, United Kingdom