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Manuela Elsen Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany

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Silja Raschke Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany

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Jürgen Eckel Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany

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-induced insulin resistance ( Boström et al . 2012 a ). These results suggested a potential protective role of irisin in the development of type 2 diabetes, one of the major obesity-associated metabolic diseases. In order to investigate the relevance of irisin in

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Bernard Khoo Endocrinology, Division of Medicine, University College London, Royal Free Campus, London, UK

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Tricia Mei-Mei Tan Department of Digestion, Metabolism and Reproduction, Imperial College London, Hammersmith Campus, London, UK

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, type 2 diabetes (T2D), hypertension, hyperlipidaemia, obstructive sleep apnoea, subfertility, cancers (breast, ovary, prostate, liver, endometrium and colon) and fatty liver disease/steatohepatitis leading to cirrhosis and liver failure. Key drivers of

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Yolanda Diz-Chaves Laboratory of Endocrinology, Center for Biomedical Research – CINBIO, University of Vigo, Vigo, Spain
Instituto de Investigación Sanitaria Galicia Sur – IISGS, Vigo, Spain

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Manuel Gil-Lozano Laboratory of Endocrinology, Center for Biomedical Research – CINBIO, University of Vigo, Vigo, Spain
Instituto de Investigación Sanitaria Galicia Sur – IISGS, Vigo, Spain

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Laura Toba Laboratory of Endocrinology, Center for Biomedical Research – CINBIO, University of Vigo, Vigo, Spain
Instituto de Investigación Sanitaria Galicia Sur – IISGS, Vigo, Spain

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Juan Fandiño Laboratory of Endocrinology, Center for Biomedical Research – CINBIO, University of Vigo, Vigo, Spain
Instituto de Investigación Sanitaria Galicia Sur – IISGS, Vigo, Spain

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Hugo Ogando Laboratory of Endocrinology, Center for Biomedical Research – CINBIO, University of Vigo, Vigo, Spain
Instituto de Investigación Sanitaria Galicia Sur – IISGS, Vigo, Spain

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Lucas C González-Matías Laboratory of Endocrinology, Center for Biomedical Research – CINBIO, University of Vigo, Vigo, Spain
Instituto de Investigación Sanitaria Galicia Sur – IISGS, Vigo, Spain

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Federico Mallo Laboratory of Endocrinology, Center for Biomedical Research – CINBIO, University of Vigo, Vigo, Spain
Instituto de Investigación Sanitaria Galicia Sur – IISGS, Vigo, Spain

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nervous system (SNS) activation, favours the accumulation of visceral fat and contributes to the clinical presentation of visceral obesity, type 2 diabetes mellitus (DM2) and related cardiometabolic complications. In addition, both circulating and local

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Mohammed Bensellam Garvan Institute of Medical Research, Sydney, New South Wales, Australia
Université Catholique de Louvain, Institut de Recherche Expérimentale et Clinique, Pôle d’Endocrinologie, Diabète et Nutrition, Brussels, Belgium

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Jean-Christophe Jonas Université Catholique de Louvain, Institut de Recherche Expérimentale et Clinique, Pôle d’Endocrinologie, Diabète et Nutrition, Brussels, Belgium

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D Ross Laybutt Garvan Institute of Medical Research, Sydney, New South Wales, Australia
St Vincent’s Clinical School, UNSW Sydney, Sydney, New South Wales, Australia

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animal and human studies suggest that mature β-cells could regress backwards to a precursor-like stage and/or transdifferentiate into other islet cells in type 2 diabetes. Interestingly, cellular differentiation is not unidirectional. Indeed

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Prabhakara R Nagareddy Department of Nutrition Sciences, University of Alabama, Birmingham, UK

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Sunil K Noothi Department of Nutrition Sciences, University of Alabama, Birmingham, UK

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Michelle C Flynn Division of Immunometabolism, Baker Heart and Diabetes Institute, Melbourne, Australia
Department of Immunology, Monash University, Melbourne, Australia

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Andrew J Murphy Division of Immunometabolism, Baker Heart and Diabetes Institute, Melbourne, Australia
Department of Immunology, Monash University, Melbourne, Australia

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such as diabetes and metabolic syndrome to promote an exacerbated myelopoietic phenotype. The mechanisms of each of these risk factors in relation to myeloid-driven CAD are summarized in Fig. 1 (modified from Murphy & Tall 2016 ) and detailed below

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Weiwei Xu Section of Endocrinology and Metabolism, Department of Medicine, Diabetes Discovery Research and Gender Medicine Laboratory, Tulane University Health Sciences Center, School of Medicine, and Southeast Louisiana Veterans Healthcare System Medical Center, New Orleans, Louisiana, USA

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Jamie Morford Section of Endocrinology and Metabolism, Department of Medicine, Diabetes Discovery Research and Gender Medicine Laboratory, Tulane University Health Sciences Center, School of Medicine, and Southeast Louisiana Veterans Healthcare System Medical Center, New Orleans, Louisiana, USA

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Franck Mauvais-Jarvis Section of Endocrinology and Metabolism, Department of Medicine, Diabetes Discovery Research and Gender Medicine Laboratory, Tulane University Health Sciences Center, School of Medicine, and Southeast Louisiana Veterans Healthcare System Medical Center, New Orleans, Louisiana, USA

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particularly surprising, as observational studies have implicated low testosterone levels in both the development of insulin resistance and the pathogenesis of hyperglycemia and diabetes in men, and hyperglycemia requires β cell dysfunction to develop. In the

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Andrew W Norris Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, USA

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Katie Larson Ode Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, USA

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Lina Merjaneh Division of Endocrinology & Diabetes, Seattle Children’s Hospital, Seattle, Washington, USA

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Srinath Sanda Department of Pediatrics, University of California San Francisco, San Francisco, California, USA
Diabetes Center, University of California San Francisco, San Francisco, California, USA

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Yaling Yi Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USA

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Xingshen Sun Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USA

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John F Engelhardt Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, USA
Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USA

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Rebecca L Hull Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington, USA

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Example Disease Pancreatic insufficiency risk (Ahmed et al . 2003) Diabetes risk (Adler et al . 2008) I Failed synthesis G542X Severe High High II Failed protein processing F508del Severe High High III

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Louis Potier INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France

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Ludovic Waeckel INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France

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Fréderic Fumeron INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France

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Sophie Bodin INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France

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Marinos Fysekidis INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France

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Catherine Chollet INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France

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Naima Bellili INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France

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Fabrice Bonnet INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France

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Gaëlle Gusto INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France

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Gilberto Velho INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France

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Michel Marre INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France

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François Alhenc-Gelas INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France

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Ronan Roussel INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France

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Nadine Bouby INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France
INSERM U1138, University Paris Descartes, University Pierre and Marie Curie, Diabetology, INSERM U695, Paris Diderot University, Department of Endocrinology, Institut inter Régional Pour la Santé, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France

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the DESIR study group
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obesity-related disorders have provided encouraging but still limited results ( Satterfield et al . 2003 , Laatikainen et al . 2007 ). The pathogenesis of insulin resistance and diabetes in obesity is complex and still incompletely understood. Besides

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Alex Rafacho Department of Physiological Sciences, Department of Clinical Science and Education, Institute of Bioengineering and the Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Center of Biological Sciences, Federal University of Santa Catarina (UFSC), 88040-900, Florianópolis, SC, Brazil

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Henrik Ortsäter Department of Physiological Sciences, Department of Clinical Science and Education, Institute of Bioengineering and the Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Center of Biological Sciences, Federal University of Santa Catarina (UFSC), 88040-900, Florianópolis, SC, Brazil

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Angel Nadal Department of Physiological Sciences, Department of Clinical Science and Education, Institute of Bioengineering and the Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Center of Biological Sciences, Federal University of Santa Catarina (UFSC), 88040-900, Florianópolis, SC, Brazil

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Ivan Quesada Department of Physiological Sciences, Department of Clinical Science and Education, Institute of Bioengineering and the Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Center of Biological Sciences, Federal University of Santa Catarina (UFSC), 88040-900, Florianópolis, SC, Brazil

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effects, including peripheral insulin resistance (IR) and glucose intolerance as well as overt hyperglycaemia and diabetes. These side effects are observed particularly in susceptible individuals such as pregnant women, obese subjects, IR individuals or

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Noèlia Téllez CIBER of Diabetes and Metabolic Diseases, Bellvitge Biomedical Research Institute, Endocrine Unit, Department of Clinical Sciences, CIBERDEM, Barcelona, Spain
CIBER of Diabetes and Metabolic Diseases, Bellvitge Biomedical Research Institute, Endocrine Unit, Department of Clinical Sciences, CIBERDEM, Barcelona, Spain
CIBER of Diabetes and Metabolic Diseases, Bellvitge Biomedical Research Institute, Endocrine Unit, Department of Clinical Sciences, CIBERDEM, Barcelona, Spain

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Eduard Montanya CIBER of Diabetes and Metabolic Diseases, Bellvitge Biomedical Research Institute, Endocrine Unit, Department of Clinical Sciences, CIBERDEM, Barcelona, Spain
CIBER of Diabetes and Metabolic Diseases, Bellvitge Biomedical Research Institute, Endocrine Unit, Department of Clinical Sciences, CIBERDEM, Barcelona, Spain
CIBER of Diabetes and Metabolic Diseases, Bellvitge Biomedical Research Institute, Endocrine Unit, Department of Clinical Sciences, CIBERDEM, Barcelona, Spain
CIBER of Diabetes and Metabolic Diseases, Bellvitge Biomedical Research Institute, Endocrine Unit, Department of Clinical Sciences, CIBERDEM, Barcelona, Spain

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Introduction β-cell mass reduction is a central event in the development of types 1 and 2 diabetes, and β-cell regeneration is a potentially curative treatment for the disease. Strategies aiming to regenerate β-cell mass include stimulation of

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