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  1. Article ; Online: Glucose metabolism and pyruvate carboxylase enhance glutathione synthesis and restrict oxidative stress in pancreatic islets.

    Fu, Accalia / van Rooyen, Lara / Evans, Lindsay / Armstrong, Nina / Avizonis, Daina / Kin, Tatsuya / Bird, Gregory H / Reddy, Anita / Chouchani, Edward T / Liesa-Roig, Marc / Walensky, Loren D / Shapiro, A M James / Danial, Nika N

    Cell reports

    2021  Volume 37, Issue 8, Page(s) 110037

    Abstract: Glucose metabolism modulates the islet β cell responses to diabetogenic stress, including inflammation. Here, we probed the metabolic mechanisms that underlie the protective effect of glucose in inflammation by interrogating the metabolite profiles of ... ...

    Abstract Glucose metabolism modulates the islet β cell responses to diabetogenic stress, including inflammation. Here, we probed the metabolic mechanisms that underlie the protective effect of glucose in inflammation by interrogating the metabolite profiles of primary islets from human donors and identified de novo glutathione synthesis as a prominent glucose-driven pro-survival pathway. We find that pyruvate carboxylase is required for glutathione synthesis in islets and promotes their antioxidant capacity to counter inflammation and nitrosative stress. Loss- and gain-of-function studies indicate that pyruvate carboxylase is necessary and sufficient to mediate the metabolic input from glucose into glutathione synthesis and the oxidative stress response. Altered redox metabolism and cellular capacity to replenish glutathione pools are relevant in multiple pathologies beyond obesity and diabetes. Our findings reveal a direct interplay between glucose metabolism and glutathione biosynthesis via pyruvate carboxylase. This metabolic axis may also have implications in other settings where sustaining glutathione is essential.
    MeSH term(s) Adult ; Animals ; Antioxidants/physiology ; Female ; Glucose/metabolism ; Glutathione/biosynthesis ; Glutathione/metabolism ; Humans ; Insulin/metabolism ; Islets of Langerhans/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Oxidation-Reduction ; Oxidative Stress/physiology ; Primary Cell Culture ; Pyruvate Carboxylase/metabolism
    Chemical Substances Antioxidants ; Insulin ; Pyruvate Carboxylase (EC 6.4.1.1) ; Glutathione (GAN16C9B8O) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2021-11-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2021.110037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Magpie Trial in the UK

    Armstrong Nina / Spark Patsy / Smyth Rebecca MD / Duley Lelia

    BMC Pregnancy and Childbirth, Vol 9, Iss 1, p

    methods and additional data for women and children at 2 years following pregnancy complicated by pre-eclampsia

    2009  Volume 15

    Abstract: Abstract Background The Magpie Trial, a randomised trial comparing magnesium sulphate with placebo for women with pre-eclampsia. This paper describes methods used for follow up in the UK, and presents additional data collected. Methods In the UK 774 ... ...

    Abstract Abstract Background The Magpie Trial, a randomised trial comparing magnesium sulphate with placebo for women with pre-eclampsia. This paper describes methods used for follow up in the UK, and presents additional data collected. Methods In the UK 774 women and their 827 children were included; excluded were women discharged without a surviving child and families who opted out. General practitioners were sent a questionnaire when the child was around 18 months old. When the child was two years, or older, questionnaires asking about the health of the women and children were posted to families. A sample of families was offered a home visit, during which the child was assessed using the Bayley Scales of Infant Development. Results Of the women, 12 were lost to follow up and three died. Of the children, 12 were lost to follow up, 5 were excluded and 19 died. General practitioners returned 688/759 (91%) questionnaires, as did 619/759 (82%) women. Responses were largely comparable. 32 women had serious morbidity potentially related to pre-eclampsia. 30% of children were reported to have been admitted to hospital. There were no clear differences between the randomised groups in the child's behaviour, women's fertility or use of health service resources. Conclusion Data presented here provide further reassurance about the longer term safety of magnesium sulphate when used for women with pre-eclampsia. Postal questionnaires in the UK to assess the longer term health and wellbeing of women and children recruited to trials are feasible, and can achieve a high response rate. Responses from families and general practitioners were comparable Trial registration Trial registration number of the Magpie Trial [ISRCTN86938761]
    Keywords Gynecology and obstetrics ; RG1-991 ; Medicine ; R ; DOAJ:Gynecology and Obstetrics ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 360
    Language English
    Publishing date 2009-04-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Magpie Trial in the UK: methods and additional data for women and children at 2 years following pregnancy complicated by pre-eclampsia.

    Smyth, Rebecca M D / Spark, Patsy / Armstrong, Nina / Duley, Lelia

    BMC pregnancy and childbirth

    2009  Volume 9, Page(s) 15

    Abstract: Background: The Magpie Trial, a randomised trial comparing magnesium sulphate with placebo for women with pre-eclampsia. This paper describes methods used for follow up in the UK, and presents additional data collected.: Methods: In the UK 774 women ... ...

    Abstract Background: The Magpie Trial, a randomised trial comparing magnesium sulphate with placebo for women with pre-eclampsia. This paper describes methods used for follow up in the UK, and presents additional data collected.
    Methods: In the UK 774 women and their 827 children were included; excluded were women discharged without a surviving child and families who opted out. General practitioners were sent a questionnaire when the child was around 18 months old. When the child was two years, or older, questionnaires asking about the health of the women and children were posted to families. A sample of families was offered a home visit, during which the child was assessed using the Bayley Scales of Infant Development.
    Results: Of the women, 12 were lost to follow up and three died. Of the children, 12 were lost to follow up, 5 were excluded and 19 died. General practitioners returned 688/759 (91%) questionnaires, as did 619/759 (82%) women. Responses were largely comparable. 32 women had serious morbidity potentially related to pre-eclampsia. 30% of children were reported to have been admitted to hospital. There were no clear differences between the randomised groups in the child's behaviour, women's fertility or use of health service resources.
    Conclusion: Data presented here provide further reassurance about the longer term safety of magnesium sulphate when used for women with pre-eclampsia. Postal questionnaires in the UK to assess the longer term health and wellbeing of women and children recruited to trials are feasible, and can achieve a high response rate. Responses from families and general practitioners were comparable
    MeSH term(s) Age Factors ; Anticonvulsants/therapeutic use ; Child Behavior Disorders/chemically induced ; Child Behavior Disorders/epidemiology ; Child, Preschool ; Female ; Follow-Up Studies ; Health Services/statistics & numerical data ; Health Surveys ; Humans ; Infant ; Infertility/chemically induced ; Infertility/epidemiology ; Magnesium Sulfate/therapeutic use ; Physicians, Family ; Pre-Eclampsia/drug therapy ; Pre-Eclampsia/epidemiology ; Pregnancy ; Randomized Controlled Trials as Topic ; Research Design ; Surveys and Questionnaires ; Treatment Outcome ; United Kingdom/epidemiology
    Chemical Substances Anticonvulsants ; Magnesium Sulfate (7487-88-9)
    Language English
    Publishing date 2009-04-14
    Publishing country England
    Document type Journal Article ; Multicenter Study ; Randomized Controlled Trial
    ISSN 1471-2393
    ISSN (online) 1471-2393
    DOI 10.1186/1471-2393-9-15
    Database MEDical Literature Analysis and Retrieval System OnLINE

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