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Louise Grahnemo Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden

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Caroline Jochems Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden
Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden

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Annica Andersson Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden

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Cecilia Engdahl Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden
Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden

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Claes Ohlsson Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden

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Ulrika Islander Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden

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Hans Carlsten Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden

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Introduction Glucocorticoids are frequently used for the treatment of noninfectious and autoimmune inflammation as, amongst other mechanisms, they can suppress lymphocytes ( Chantler et al . 2003 , Busillo & Cidlowski 2013 ). Prolonged use of

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S Khan Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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D E W Livingstone Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Centre for Discovery Brain Science, University of Edinburgh, Hugh Robson Building, Edinburgh, UK

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A Zielinska College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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C L Doig Department of Biosciences, School of Science & Technology, Nottingham Trent University, Nottingham, UK

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D F Cobice Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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C L Esteves Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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J T Y Man Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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N Z M Homer Mass Spectrometry Core Laboratory, Edinburgh Clinical Research Facility, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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J R Seckl Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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C L MacKay SIRCAMS, School of Chemistry, University of Edinburgh, Joseph Black Building, King's Buildings, Edinburgh, UK

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S P Webster Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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G G Lavery Department of Biosciences, School of Science & Technology, Nottingham Trent University, Nottingham, UK

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K E Chapman Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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B R Walker Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Clinical & Translational Research Institute, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK

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R Andrew Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Mass Spectrometry Core Laboratory, Edinburgh Clinical Research Facility, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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Introduction 11β-Hydroxysteroid dehydrogenase 1 (11βHSD1) generates active 11-hydroxy glucocorticoids (cortisol (human), corticosterone (rodent and human)) from intrinsically inert 11-keto steroids (cortisone, 11-dehydrocorticosterone (11DHC

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Dawn E W Livingstone University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, UK
Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK

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Emma M Di Rollo University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, UK

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Tracy C-S Mak University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, UK

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Karen Sooy University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, UK

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Brian R Walker University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, UK

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Ruth Andrew University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, UK

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types 1 and 2 being best characterised ( Godoy et al. 2011 ). The 5α-dihydro metabolite (DHT) is a more potent androgen than testosterone. The 3α,5α-metabolites of glucocorticoids retain some anti-inflammatory properties of the original steroid

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Young Hoon Son Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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Seok-Jin Lee Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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Ki-Baek Lee Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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Jin-Haeng Lee Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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Eui Man Jeong Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea
Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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Sun Gun Chung Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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Sang-Chul Park Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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In-Gyu Kim Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea
Department of Biochemistry and Molecular Biology, Institute of Human–Environment Interface Biology, Department of Rehabilitation Medicine, Seoul National University College of Medicine, 103 Daehak‐ro, Jongno‐Gu, Seoul 110‐799, Korea

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Introduction Glucocorticoids have diverse and tissue-specific effects on cellular metabolism. During metabolic stress, such as starvation, glucocorticoids promote degradation and suppress synthesis of muscle proteins in the skeletal muscle, thereby

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Craig L Doig School of Clinical and Experimental Medicine, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham B15 2TT, UK

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Jamila Bashir School of Clinical and Experimental Medicine, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham B15 2TT, UK

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Agnieszka E Zielinska School of Clinical and Experimental Medicine, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham B15 2TT, UK

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Mark S Cooper School of Clinical and Experimental Medicine, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham B15 2TT, UK

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Paul M Stewart School of Clinical and Experimental Medicine, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham B15 2TT, UK

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Gareth G Lavery School of Clinical and Experimental Medicine, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham B15 2TT, UK

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Introduction The endogenous glucocorticoid (GC) concentrations are determined by the activity of the hypothalamic–pituitary–adrenal axis, with tissue and intracellular exposure further augmented through the activity of the enzyme 11β

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Zhenguang Zhang University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Agnes E Coutinho University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Tak Yung Man University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Tiina M J Kipari Centre for Genomic and Experimental Medicine, MRC Institute of Genetic and Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, UK

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Patrick W F Hadoke University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Donald M Salter Centre for Genomic and Experimental Medicine, MRC Institute of Genetic and Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, UK

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Jonathan R Seckl University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Karen E Chapman University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Introduction Glucocorticoids exert anti-inflammatory effects both in vivo and in vitro . Whilst the potent effects of synthetic glucocorticoids have been widely exploited clinically to treat inflammatory disease, including rheumatoid

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A McMaster Medicine, Faculty of Life Sciences, Centre for Molecular
Medicine, Faculty of Life Sciences, Centre for Molecular

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T Chambers Medicine, Faculty of Life Sciences, Centre for Molecular

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Q-J Meng Medicine, Faculty of Life Sciences, Centre for Molecular

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S Grundy Medicine, Faculty of Life Sciences, Centre for Molecular

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A S I Loudon Medicine, Faculty of Life Sciences, Centre for Molecular

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R Donn Medicine, Faculty of Life Sciences, Centre for Molecular
Medicine, Faculty of Life Sciences, Centre for Molecular

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D W Ray Medicine, Faculty of Life Sciences, Centre for Molecular

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Introduction Glucocorticoid hormones exert a wide diversity of effects in target tissues. Their activity has been typically explored using a limited number of timed end points, both in vivo and in vitro , and using such approaches a variety of

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Ying Sze Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK
The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, UK

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Joana Fernandes The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, UK

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Zofia M Kołodziejczyk Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK

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Paula J Brunton Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK
The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, UK
Zhejiang University-University of Edinburgh Institute, International Campus, Haining, Zhejiang, P.R. China

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( Pariante & Lightman 2008 ). The HPA axis is the primary neuroendocrine stress response system. It is activated following perturbations to normal homeostasis, resulting in increased secretion of glucocorticoids from the adrenal gland, which mobilises energy

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Nan Yang Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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Giorgio Caratti Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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Louise M Ince Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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Toryn M Poolman Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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Peter J Trebble Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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Cathy M Holt Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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David W Ray Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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Laura C Matthews Manchester Centre for Nuclear Hormone Research in Disease and Institute of Human Development, Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

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Introduction Glucocorticoids (Gc) are potent anti-inflammatory agents and are widely prescribed for the treatment of a range of inflammatory and immune diseases including rheumatoid arthritis and asthma ( McMaster & Ray 2007 , Barnes & Adcock 2009

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Nikolaos Nikolaou Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Anastasia Arvaniti Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK
Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK

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Nathan Appanna Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Anna Sharp Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Beverly A Hughes Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham, UK

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Dena Digweed Diurnal Ltd, Cardiff, UK

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Martin J Whitaker Diurnal Ltd, Cardiff, UK

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Richard Ross Department of Oncology and Metabolism, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK

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Wiebke Arlt Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham, UK
NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK

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Trevor M Penning Department of Systems Pharmacology & Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA

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Karen Morris Biochemistry Department, Manchester University NHS Trust, Manchester, UK

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Sherly George Biochemistry Department, Manchester University NHS Trust, Manchester, UK

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Brian G Keevil Biochemistry Department, Manchester University NHS Trust, Manchester, UK

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Leanne Hodson Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Laura L Gathercole Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK
Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK

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Jeremy W Tomlinson Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK

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Introduction Glucocorticoids (GCs) are steroid hormones that are released in response to stress and play a crucial role in inflammation and in carbohydrate, lipid and protein metabolism. Within key metabolic target tissues, notably the liver

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