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Topics {✒️}

pcmv6-xl4-hnf4α expression vector open access article north-east-south gradient anti-ha-mouse antibody binding nord-trondelag health surveys nord-trøndelag county council receptor-beta-induced increases 6alpha-hydroxy bile acids pre-publication history glucose-stimulated insulin secretion nf1c protein-oligonucleotide complex nf1c protein-oligonucleotide complexes adolescence-cross sectional study adolescence cross-sectional study informed consent form lipid-activated nuclear receptors lower homa-ir index empty basic-pgl3 vector helena cross-sectional study higher homa-ir index obesity-/t2dm-related quantitative phenotypes transfected prl-cmv vector anti-ha tag antibody genome-wide association studies significant inter-group differences medical research ethics lxr agonists' anti-atherosclerotic bmc med genet lxrβ transcription level t2dm-related quantitative phenotypes javier romeo article download pdf orphan nuclear receptors norwegian regional committee article number 144 t2dm case-control individuals lxrβ snp-disorder association hormone laboratory entire genetic variability privacy choices/manage cookies case-control study relevant transcription factor common genetic polymorphisms universitaire de lille nuclear receptors involved case fatality rates empty basic-pgl3 human jeg3 choriocarcinoma jean dallongeville & aline meirhaeghe potential therapeutic agents

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WebPage:
      mainEntity:
         headline:Suggestive evidence of associations between liver X receptor β polymorphisms with type 2 diabetes mellitus and obesity in three cohort studies: HUNT2 (Norway), MONICA (France) and HELENA (Europe)
         description:The liver X receptors (LXR) α and β regulate lipid and carbohydrate homeostasis and inflammation. Lxrβ -/- mice are glucose intolerant and at the same time lean. We aimed to assess the associations between single nucleotide polymorphisms (SNPs) in LXRβ and risk of type 2 diabetes mellitus (T2DM), obesity and related traits in 3 separate cohort studies. Twenty LXRβ SNPs were identified by sequencing and genotyped in the HUNT2 adult nested case-control study for T2DM (n = 835 cases/1986 controls). Five tag-SNPs (rs17373080, rs2695121, rs56151148, rs2303044 and rs3219281), covering 99.3% of the entire common genetic variability of the LXRβ gene were identified and genotyped in the French MONICA adult study (n = 2318) and the European adolescent HELENA cross-sectional study (n = 1144). In silico and in vitro functionality studies were performed. We identified suggestive or significant associations between rs17373080 and the risk of (i) T2DM in HUNT2 (OR = 0.82, p = 0.03), (ii) obesity in MONICA (OR = 1.26, p = 0.05) and (iii) overweight/obesity in HELENA (OR = 1.59, p = 0.002). An intron 4 SNP (rs28514894, a perfect proxy for rs17373080) could potentially create binding sites for hepatic nuclear factor 4 alpha (HNF4α) and nuclear factor 1 (NF1). The C allele of rs28514894 was associated with ~1.25-fold higher human LXRβ basal promoter activity in vitro. However, no differences between alleles in terms of DNA binding and reporter gene transactivation by HNF4α or NF1 were observed. Our results suggest that rs17373080 in LXRβ is associated with T2DM and obesity, maybe via altered LXRβ expression.
         datePublished:2010-10-12T00:00:00Z
         dateModified:2010-10-12T00:00:00Z
         pageStart:1
         pageEnd:11
         license:https://creativecommons.org/licenses/by/2.0
         sameAs:https://doi.org/10.1186/1471-2350-11-144
         keywords:
            Allelic Form
            JEG3 Cell
            HUNT2 Study
            Hepatic Nuclear Factor
            Lower Plasma Glucose Level
            Human Genetics
            Cytogenetics
            Gene Function
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                        name:Department of Endocrinology, Oslo University Hospital, Aker, Oslo, Norway
                        type:PostalAddress
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                        name:Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway
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                        name:INSERM, U744; Institut Pasteur de Lille, Univ. Lille Nord de France; UDSL, Lille, France
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               name:Kjetil Retterstol
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                     address:
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                        name:Norwegian Medical Agency, Oslo, Norway
                        type:PostalAddress
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               name:Paul R Berg
               affiliation:
                     name:The Norwegian University of Life Sciences
                     address:
                        name:Centre for Integrative Genetics, The Norwegian University of Life Sciences, Aas, Norway
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Kirsten B Holven
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                     name:University of Oslo
                     address:
                        name:Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway
                        type:PostalAddress
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               name:Jean Ferrières
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                        name:Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France
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                     name:Univ. Lille Nord de France; UDSL
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                     name:Spanish Scientific Research Council
                     address:
                        name:Immunonutrition group, Department of Metabolism and Nutrition, Institute Frio-ICTAN, Spanish Scientific Research Council, Madrid, Spain
                        type:PostalAddress
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                     address:
                        name:Department of Endocrinology, Oslo University Hospital, Aker, Oslo, Norway
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               name:Per M Thorsby
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                        name:The Hormone Laboratory, Oslo University Hospital, Aker, Oslo, Norway
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ScholarlyArticle:
      headline:Suggestive evidence of associations between liver X receptor β polymorphisms with type 2 diabetes mellitus and obesity in three cohort studies: HUNT2 (Norway), MONICA (France) and HELENA (Europe)
      description:The liver X receptors (LXR) α and β regulate lipid and carbohydrate homeostasis and inflammation. Lxrβ -/- mice are glucose intolerant and at the same time lean. We aimed to assess the associations between single nucleotide polymorphisms (SNPs) in LXRβ and risk of type 2 diabetes mellitus (T2DM), obesity and related traits in 3 separate cohort studies. Twenty LXRβ SNPs were identified by sequencing and genotyped in the HUNT2 adult nested case-control study for T2DM (n = 835 cases/1986 controls). Five tag-SNPs (rs17373080, rs2695121, rs56151148, rs2303044 and rs3219281), covering 99.3% of the entire common genetic variability of the LXRβ gene were identified and genotyped in the French MONICA adult study (n = 2318) and the European adolescent HELENA cross-sectional study (n = 1144). In silico and in vitro functionality studies were performed. We identified suggestive or significant associations between rs17373080 and the risk of (i) T2DM in HUNT2 (OR = 0.82, p = 0.03), (ii) obesity in MONICA (OR = 1.26, p = 0.05) and (iii) overweight/obesity in HELENA (OR = 1.59, p = 0.002). An intron 4 SNP (rs28514894, a perfect proxy for rs17373080) could potentially create binding sites for hepatic nuclear factor 4 alpha (HNF4α) and nuclear factor 1 (NF1). The C allele of rs28514894 was associated with ~1.25-fold higher human LXRβ basal promoter activity in vitro. However, no differences between alleles in terms of DNA binding and reporter gene transactivation by HNF4α or NF1 were observed. Our results suggest that rs17373080 in LXRβ is associated with T2DM and obesity, maybe via altered LXRβ expression.
      datePublished:2010-10-12T00:00:00Z
      dateModified:2010-10-12T00:00:00Z
      pageStart:1
      pageEnd:11
      license:https://creativecommons.org/licenses/by/2.0
      sameAs:https://doi.org/10.1186/1471-2350-11-144
      keywords:
         Allelic Form
         JEG3 Cell
         HUNT2 Study
         Hepatic Nuclear Factor
         Lower Plasma Glucose Level
         Human Genetics
         Cytogenetics
         Gene Function
      image:
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2F1471-2350-11-144/MediaObjects/12881_2010_Article_705_Fig1_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2F1471-2350-11-144/MediaObjects/12881_2010_Article_705_Fig2_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2F1471-2350-11-144/MediaObjects/12881_2010_Article_705_Fig3_HTML.jpg
      isPartOf:
         name:BMC Medical Genetics
         issn:
            1471-2350
         volumeNumber:11
         type:
            Periodical
            PublicationVolume
      publisher:
         name:BioMed Central
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Karianne Solaas
            affiliation:
                  name:Oslo University Hospital, Aker
                  address:
                     name:Department of Endocrinology, Oslo University Hospital, Aker, Oslo, Norway
                     type:PostalAddress
                  type:Organization
                  name:University of Oslo
                  address:
                     name:Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Vanessa Legry
            affiliation:
                  name:Univ. Lille Nord de France; UDSL
                  address:
                     name:INSERM, U744; Institut Pasteur de Lille, Univ. Lille Nord de France; UDSL, Lille, France
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Kjetil Retterstol
            affiliation:
                  name:Oslo University Hospital, Rikshospitalet
                  address:
                     name:The Lipid Clinic, Oslo University Hospital, Rikshospitalet, Oslo, Norway
                     type:PostalAddress
                  type:Organization
                  name:Norwegian Medical Agency
                  address:
                     name:Norwegian Medical Agency, Oslo, Norway
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Paul R Berg
            affiliation:
                  name:The Norwegian University of Life Sciences
                  address:
                     name:Centre for Integrative Genetics, The Norwegian University of Life Sciences, Aas, Norway
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Kirsten B Holven
            affiliation:
                  name:University of Oslo
                  address:
                     name:Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Jean Ferrières
            affiliation:
                  name:Toulouse University School of Medicine, Rangueil Hospital
                  address:
                     name:Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France
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            name:Philippe Amouyel
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                  name:Univ. Lille Nord de France; UDSL
                  address:
                     name:INSERM, U744; Institut Pasteur de Lille, Univ. Lille Nord de France; UDSL, Lille, France
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            name:Sigbjorn Lien
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                  name:The Norwegian University of Life Sciences
                  address:
                     name:Centre for Integrative Genetics, The Norwegian University of Life Sciences, Aas, Norway
                     type:PostalAddress
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            type:Person
            name:Javier Romeo
            affiliation:
                  name:Spanish Scientific Research Council
                  address:
                     name:Immunonutrition group, Department of Metabolism and Nutrition, Institute Frio-ICTAN, Spanish Scientific Research Council, Madrid, Spain
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                  name:Universidad Politécnica de Madrid
                  address:
                     name:Facultad de Ciencias de la Actividad Fisica y del Deporte- INEF, Universidad Politécnica de Madrid, Madrid, Spain
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Kurt Widhalm
            affiliation:
                  name:Medical University of Vienna
                  address:
                     name:Department of Paediatrics, Division of Clinical Nutrition and Prevention, Medical University of Vienna, Vienna, Austria
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Jonatan R Ruiz
            affiliation:
                  name:Karolinska Institutet
                  address:
                     name:Unit for Preventive Nutrition, Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, Stockholm, Sweden
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Jean Dallongeville
            affiliation:
                  name:Univ. Lille Nord de France; UDSL
                  address:
                     name:INSERM, U744; Institut Pasteur de Lille, Univ. Lille Nord de France; UDSL, Lille, France
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Serena Tonstad
            affiliation:
                  name:Oslo University Hospital, Ulleval
                  address:
                     name:Department of Preventive Medicine, Oslo University Hospital, Ulleval, Oslo, Norway
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Helge Rootwelt
            affiliation:
                  name:Oslo University Hospital, Rikshospitalet
                  address:
                     name:Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet, Oslo, Norway
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Bente Halvorsen
            affiliation:
                  name:Oslo University Hospital, Rikshospitalet
                  address:
                     name:Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Marit S Nenseter
            affiliation:
                  name:Oslo University Hospital, Rikshospitalet
                  address:
                     name:Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Kare I Birkeland
            affiliation:
                  name:Oslo University Hospital, Aker
                  address:
                     name:Department of Endocrinology, Oslo University Hospital, Aker, Oslo, Norway
                     type:PostalAddress
                  type:Organization
                  name:University of Oslo
                  address:
                     name:Faculty of Medicine, University of Oslo, Norway
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Per M Thorsby
            affiliation:
                  name:Oslo University Hospital, Aker
                  address:
                     name:The Hormone Laboratory, Oslo University Hospital, Aker, Oslo, Norway
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Aline Meirhaeghe
            affiliation:
                  name:Univ. Lille Nord de France; UDSL
                  address:
                     name:INSERM, U744; Institut Pasteur de Lille, Univ. Lille Nord de France; UDSL, Lille, France
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
            name:Hilde I Nebb
            affiliation:
                  name:University of Oslo
                  address:
                     name:Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
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      name:BMC Medical Genetics
      issn:
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      name:Oslo University Hospital, Aker
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         name:Department of Endocrinology, Oslo University Hospital, Aker, Oslo, Norway
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      name:University of Oslo
      address:
         name:Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway
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         name:INSERM, U744; Institut Pasteur de Lille, Univ. Lille Nord de France; UDSL, Lille, France
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      name:Oslo University Hospital, Rikshospitalet
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         name:Norwegian Medical Agency, Oslo, Norway
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         name:Centre for Integrative Genetics, The Norwegian University of Life Sciences, Aas, Norway
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         name:Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway
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         name:Facultad de Ciencias de la Actividad Fisica y del Deporte- INEF, Universidad Politécnica de Madrid, Madrid, Spain
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      name:Medical University of Vienna
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         name:The Hormone Laboratory, Oslo University Hospital, Aker, Oslo, Norway
         type:PostalAddress
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         name:INSERM, U744; Institut Pasteur de Lille, Univ. Lille Nord de France; UDSL, Lille, France
         type:PostalAddress
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            address:
               name:Department of Endocrinology, Oslo University Hospital, Aker, Oslo, Norway
               type:PostalAddress
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            name:University of Oslo
            address:
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      affiliation:
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            address:
               name:Department of Paediatrics, Division of Clinical Nutrition and Prevention, Medical University of Vienna, Vienna, Austria
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      name:Jonatan R Ruiz
      affiliation:
            name:Karolinska Institutet
            address:
               name:Unit for Preventive Nutrition, Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, Stockholm, Sweden
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      affiliation:
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            address:
               name:INSERM, U744; Institut Pasteur de Lille, Univ. Lille Nord de France; UDSL, Lille, France
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            address:
               name:Department of Preventive Medicine, Oslo University Hospital, Ulleval, Oslo, Norway
               type:PostalAddress
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      name:Helge Rootwelt
      affiliation:
            name:Oslo University Hospital, Rikshospitalet
            address:
               name:Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet, Oslo, Norway
               type:PostalAddress
            type:Organization
      name:Bente Halvorsen
      affiliation:
            name:Oslo University Hospital, Rikshospitalet
            address:
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               type:PostalAddress
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            address:
               name:Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
               type:PostalAddress
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      name:Kare I Birkeland
      affiliation:
            name:Oslo University Hospital, Aker
            address:
               name:Department of Endocrinology, Oslo University Hospital, Aker, Oslo, Norway
               type:PostalAddress
            type:Organization
            name:University of Oslo
            address:
               name:Faculty of Medicine, University of Oslo, Norway
               type:PostalAddress
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      name:Per M Thorsby
      affiliation:
            name:Oslo University Hospital, Aker
            address:
               name:The Hormone Laboratory, Oslo University Hospital, Aker, Oslo, Norway
               type:PostalAddress
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      name:Aline Meirhaeghe
      affiliation:
            name:Univ. Lille Nord de France; UDSL
            address:
               name:INSERM, U744; Institut Pasteur de Lille, Univ. Lille Nord de France; UDSL, Lille, France
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Hilde I Nebb
      affiliation:
            name:University of Oslo
            address:
               name:Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Endocrinology, Oslo University Hospital, Aker, Oslo, Norway
      name:Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway
      name:INSERM, U744; Institut Pasteur de Lille, Univ. Lille Nord de France; UDSL, Lille, France
      name:The Lipid Clinic, Oslo University Hospital, Rikshospitalet, Oslo, Norway
      name:Norwegian Medical Agency, Oslo, Norway
      name:Centre for Integrative Genetics, The Norwegian University of Life Sciences, Aas, Norway
      name:Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway
      name:Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France
      name:INSERM, U744; Institut Pasteur de Lille, Univ. Lille Nord de France; UDSL, Lille, France
      name:Centre for Integrative Genetics, The Norwegian University of Life Sciences, Aas, Norway
      name:Immunonutrition group, Department of Metabolism and Nutrition, Institute Frio-ICTAN, Spanish Scientific Research Council, Madrid, Spain
      name:Facultad de Ciencias de la Actividad Fisica y del Deporte- INEF, Universidad Politécnica de Madrid, Madrid, Spain
      name:Department of Paediatrics, Division of Clinical Nutrition and Prevention, Medical University of Vienna, Vienna, Austria
      name:Unit for Preventive Nutrition, Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, Stockholm, Sweden
      name:INSERM, U744; Institut Pasteur de Lille, Univ. Lille Nord de France; UDSL, Lille, France
      name:Department of Preventive Medicine, Oslo University Hospital, Ulleval, Oslo, Norway
      name:Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet, Oslo, Norway
      name:Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
      name:Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
      name:Department of Endocrinology, Oslo University Hospital, Aker, Oslo, Norway
      name:Faculty of Medicine, University of Oslo, Norway
      name:The Hormone Laboratory, Oslo University Hospital, Aker, Oslo, Norway
      name:INSERM, U744; Institut Pasteur de Lille, Univ. Lille Nord de France; UDSL, Lille, France
      name:Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway

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