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Selina Mäkinen Minerva Foundation Institute for Medical Research, Tukholmankatu, Helsinki, Finland
Department of Medicine, University of Helsinki and Helsinki University Hospital, Haartmaninkatu, Helsinki, Finland

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Neeta Datta Minerva Foundation Institute for Medical Research, Tukholmankatu, Helsinki, Finland
Department of Medicine, University of Helsinki and Helsinki University Hospital, Haartmaninkatu, Helsinki, Finland

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Savithri Rangarajan Pam Gene International B.V., Wolvenhoek, BJ ´s-Hertogenbosch, The Netherlands

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Yen H Nguyen Minerva Foundation Institute for Medical Research, Tukholmankatu, Helsinki, Finland
Department of Medicine, University of Helsinki and Helsinki University Hospital, Haartmaninkatu, Helsinki, Finland

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Vesa M Olkkonen Minerva Foundation Institute for Medical Research, Tukholmankatu, Helsinki, Finland
Department of Anatomy, Faculty of Medicine, Haartmaninkatu, University of Helsinki, Helsinki, Finland

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Aino Latva-Rasku Turku PET Centre, University of Turku, Kiinamyllynkatu, Turku, Finland
Turku PET Centre, Turku University Hospital, Kiinamyllynkatu, Turku, Finland

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Pirjo Nuutila Turku PET Centre, University of Turku, Kiinamyllynkatu, Turku, Finland
Turku PET Centre, Turku University Hospital, Kiinamyllynkatu, Turku, Finland

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Markku Laakso Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Puijonlaaksontie, Kuopio, Finland

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Heikki A Koistinen Minerva Foundation Institute for Medical Research, Tukholmankatu, Helsinki, Finland
Department of Medicine, University of Helsinki and Helsinki University Hospital, Haartmaninkatu, Helsinki, Finland

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Introduction Genetic variants in the insulin signalling pathway contribute to increased risk for type 2 diabetes ( Manning et al. 2012 , 2017 ). One example of an insulin resistance-associated gene is a missense variant p.P50T of AKT2

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Avraham I Jacob
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Miriam Horovitz-Fried
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Shlomit Aga-Mizrachi
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Tamar Brutman-Barazani
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Hana Okhrimenko
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Yehiel Zick Mina and Everard Goodman Faculty of Life Sciences, Department of Molecular Cell Biology, Gonda Diagnostic Center, Bar-Ilan University, Ramat-Gan 52900, Israel

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Chaya Brodie
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Sanford R Sampson
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Introduction The protein kinase C (PKC) family of serine–threonine kinases plays important roles in many intracellular signaling events, cell growth, and differentiation ( Nishizuka 1988 , 1989 , 1992 ). It is generally accepted that the enzymes

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Matei Bolborea Rowett Institute of Nutrition and Health, School of Life Sciences, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK
Rowett Institute of Nutrition and Health, School of Life Sciences, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK

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Gisela Helfer Rowett Institute of Nutrition and Health, School of Life Sciences, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK

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Francis J P Ebling Rowett Institute of Nutrition and Health, School of Life Sciences, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK

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Perry Barrett Rowett Institute of Nutrition and Health, School of Life Sciences, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK

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-dependent signalling mechanism ( de Vries et al . 2014 , Wittmann et al . 2014 ), and long-day photoperiods, which are caused by thyroid stimulating hormone (TSH) of pars tuberalis origin ( Hanon et al . 2008 , Nakao et al . 2008 , Ono et al . 2008 , Helfer

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Kathryn L Auld
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Stephen P Berasi Pfizer Global Biotherapeutics Technologies, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer Oncology Research and Development, Former Wyeth Colleagues, Cambridge, Massachusetts, USA

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Yan Liu Pfizer Global Biotherapeutics Technologies, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer Oncology Research and Development, Former Wyeth Colleagues, Cambridge, Massachusetts, USA

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Michael Cain Pfizer Global Biotherapeutics Technologies, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer Oncology Research and Development, Former Wyeth Colleagues, Cambridge, Massachusetts, USA

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Ying Zhang Pfizer Global Biotherapeutics Technologies, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer Oncology Research and Development, Former Wyeth Colleagues, Cambridge, Massachusetts, USA

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Christine Huard Pfizer Global Biotherapeutics Technologies, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer Oncology Research and Development, Former Wyeth Colleagues, Cambridge, Massachusetts, USA

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Shoichi Fukayama Pfizer Global Biotherapeutics Technologies, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer Oncology Research and Development, Former Wyeth Colleagues, Cambridge, Massachusetts, USA

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Jing Zhang
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Sung Choe
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Wenyan Zhong Pfizer Global Biotherapeutics Technologies, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer Oncology Research and Development, Former Wyeth Colleagues, Cambridge, Massachusetts, USA

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Bheem M Bhat Pfizer Global Biotherapeutics Technologies, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer Oncology Research and Development, Former Wyeth Colleagues, Cambridge, Massachusetts, USA

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Ramesh A Bhat Pfizer Global Biotherapeutics Technologies, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer Oncology Research and Development, Former Wyeth Colleagues, Cambridge, Massachusetts, USA

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Eugene L Brown Pfizer Global Biotherapeutics Technologies, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer Oncology Research and Development, Former Wyeth Colleagues, Cambridge, Massachusetts, USA

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Robert V Martinez Pfizer Global Biotherapeutics Technologies, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer BioTherapeutics Research and Development, Pfizer Oncology Research and Development, Former Wyeth Colleagues, Cambridge, Massachusetts, USA

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ERRα acts as an inhibitor of osteoblast differentiation in vitro ( Teyssier et al . 2009 ). The Wnt pathway is another important player in bone development (reviewed in Bodine & Komm (2006) ). During canonical Wnt/β-catenin signaling, Wnt ligands

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Lekha Jain Liggins Institute, University of Auckland, Auckland, New Zealand

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Tayaza Fadason Liggins Institute, University of Auckland, Auckland, New Zealand

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William Schierding Liggins Institute, University of Auckland, Auckland, New Zealand

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Mark H Vickers Liggins Institute, University of Auckland, Auckland, New Zealand

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Justin M O’Sullivan Liggins Institute, University of Auckland, Auckland, New Zealand

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Jo K Perry Liggins Institute, University of Auckland, Auckland, New Zealand

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& Melmed 2017 ). Secretion of GH is positively modulated by GH releasing hormone (GHRH), ghrelin, and negatively by somatostatin. Insulin-like growth factor (IGF-1) is a key mediator of GH actions. Compromised GH/IGF-1 signalling is associated with several

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Caroline M Gorvin Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
Oxford NIHR Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK
Institute of Metabolism and Systems Research (IMSR) & Centre for Endocrinology, Diabetes and Metabolism (CEDAM), Birmingham Health Partners, University of Birmingham, Birmingham, UK
Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham, UK

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Paul J Newey Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
Division of Molecular & Clinical Medicine (MCM), University of Dundee, Jacqui Wood Cancer Centre, Dundee, UK

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Rajesh V Thakker Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
Oxford NIHR Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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potentially, simultaneous interaction with multiple signalling kinases ( Haxholm et al. 2015 , Bugge et al. 2016 ). Hormone binding to the ECD activates conformational changes within the TMD and ICD, allowing separation of the ICDs and initiating

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Carolina S Martinez Facultad de Farmacia y Bioquímica, Department of Geriatrics (A.B.), Instituto de Biología y Medicina Experimental (CONICET), Instituto de Química y Fisicoquímica Biológicas (UBA‐CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina

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Verónica G Piazza Facultad de Farmacia y Bioquímica, Department of Geriatrics (A.B.), Instituto de Biología y Medicina Experimental (CONICET), Instituto de Química y Fisicoquímica Biológicas (UBA‐CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina

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María E Díaz Facultad de Farmacia y Bioquímica, Department of Geriatrics (A.B.), Instituto de Biología y Medicina Experimental (CONICET), Instituto de Química y Fisicoquímica Biológicas (UBA‐CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina

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Ravneet K Boparai Facultad de Farmacia y Bioquímica, Department of Geriatrics (A.B.), Instituto de Biología y Medicina Experimental (CONICET), Instituto de Química y Fisicoquímica Biológicas (UBA‐CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina

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Oge Arum Facultad de Farmacia y Bioquímica, Department of Geriatrics (A.B.), Instituto de Biología y Medicina Experimental (CONICET), Instituto de Química y Fisicoquímica Biológicas (UBA‐CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina

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María C Ramírez Facultad de Farmacia y Bioquímica, Department of Geriatrics (A.B.), Instituto de Biología y Medicina Experimental (CONICET), Instituto de Química y Fisicoquímica Biológicas (UBA‐CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina

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Lorena González Facultad de Farmacia y Bioquímica, Department of Geriatrics (A.B.), Instituto de Biología y Medicina Experimental (CONICET), Instituto de Química y Fisicoquímica Biológicas (UBA‐CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina

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Damasia Becú-Villalobos Facultad de Farmacia y Bioquímica, Department of Geriatrics (A.B.), Instituto de Biología y Medicina Experimental (CONICET), Instituto de Química y Fisicoquímica Biológicas (UBA‐CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina

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Andrzej Bartke Facultad de Farmacia y Bioquímica, Department of Geriatrics (A.B.), Instituto de Biología y Medicina Experimental (CONICET), Instituto de Química y Fisicoquímica Biológicas (UBA‐CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina

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Daniel Turyn Facultad de Farmacia y Bioquímica, Department of Geriatrics (A.B.), Instituto de Biología y Medicina Experimental (CONICET), Instituto de Química y Fisicoquímica Biológicas (UBA‐CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina

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Johanna G Miquet Facultad de Farmacia y Bioquímica, Department of Geriatrics (A.B.), Instituto de Biología y Medicina Experimental (CONICET), Instituto de Química y Fisicoquímica Biológicas (UBA‐CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina

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Ana I Sotelo Facultad de Farmacia y Bioquímica, Department of Geriatrics (A.B.), Instituto de Biología y Medicina Experimental (CONICET), Instituto de Química y Fisicoquímica Biológicas (UBA‐CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina

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, which phosphorylates GHR on multiple intracellular tyrosine residues ( Brooks & Waters 2010 , Sedek et al . 2014 ). These residues become anchoring sites for several signaling mediators, among which signal transducer and activator of transcription 5b

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Marta Labeur Department of Neuroendocrinology, Max Planck Institute of Psychiatry, 80804 Munich, Germany

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Barbara Wölfel Department of Neuroendocrinology, Max Planck Institute of Psychiatry, 80804 Munich, Germany

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Johanna Stalla Department of Neuroendocrinology, Max Planck Institute of Psychiatry, 80804 Munich, Germany

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Günter K Stalla Department of Neuroendocrinology, Max Planck Institute of Psychiatry, 80804 Munich, Germany

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/CRHR1 signaling in corticotrope cells ( Paez-Pereda et al . 2001 ) and induces BMP4, which participates in the antiproliferative effects of RA ( Giacomini et al . 2006 ). Moreover, treatment of dogs with ACTH-secreting tumors with RA controls

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William J Stanley St. Vincent’s Institute of Medical Research, Melbourne, Australia
Department of Medicine, St. Vincent’s Hospital, The University of Melbourne, Melbourne, Australia

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Prerak M Trivedi St. Vincent’s Institute of Medical Research, Melbourne, Australia
Department of Medicine, St. Vincent’s Hospital, The University of Melbourne, Melbourne, Australia

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Andrew P Sutherland St. Vincent’s Institute of Medical Research, Melbourne, Australia

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Helen E Thomas St. Vincent’s Institute of Medical Research, Melbourne, Australia
Department of Medicine, St. Vincent’s Hospital, The University of Melbourne, Melbourne, Australia

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Esteban N Gurzov St. Vincent’s Institute of Medical Research, Melbourne, Australia
Department of Medicine, St. Vincent’s Hospital, The University of Melbourne, Melbourne, Australia
ULB Center for Diabetes Research, Universite Libre de Bruxelles (ULB), Brussels, Belgium

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( Thomas et al . 2006 , Gurzov & Eizirik 2011 , Moore et al . 2011 ). Pro-apoptotic gene expression occurs by cytokine-stimulated cell signalling cascades that activate a variety of kinases and transcription factors, predominantly by phosphorylation

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Su M Hlaing Departments of Internal Medicine, Health and Life Sciences, Division of Endocrinology, Department of Medicine, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059, USA

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Leah A Garcia Departments of Internal Medicine, Health and Life Sciences, Division of Endocrinology, Department of Medicine, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059, USA

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Jaime R Contreras Departments of Internal Medicine, Health and Life Sciences, Division of Endocrinology, Department of Medicine, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059, USA

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Keith C Norris Departments of Internal Medicine, Health and Life Sciences, Division of Endocrinology, Department of Medicine, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059, USA

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Monica G Ferrini Departments of Internal Medicine, Health and Life Sciences, Division of Endocrinology, Department of Medicine, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059, USA
Departments of Internal Medicine, Health and Life Sciences, Division of Endocrinology, Department of Medicine, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059, USA
Departments of Internal Medicine, Health and Life Sciences, Division of Endocrinology, Department of Medicine, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059, USA

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Jorge N Artaza Departments of Internal Medicine, Health and Life Sciences, Division of Endocrinology, Department of Medicine, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059, USA
Departments of Internal Medicine, Health and Life Sciences, Division of Endocrinology, Department of Medicine, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059, USA
Departments of Internal Medicine, Health and Life Sciences, Division of Endocrinology, Department of Medicine, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059, USA
Departments of Internal Medicine, Health and Life Sciences, Division of Endocrinology, Department of Medicine, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059, USA

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. 2007 ). The aim of this study was to test the hypothesis that 1,25-D 3 promotes myocardiac cell differentiation through inhibition of the WNT signaling pathway and to determine the associated molecular mechanism(s) in a well-known and widely used heart

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