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Astrid Chamson-Reig Lawson Health Research Institute, Medicine, Microbiology and Immunology, Paediatrics, St Joseph's Health Care, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2 Departments of

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Edith J Arany Lawson Health Research Institute, Medicine, Microbiology and Immunology, Paediatrics, St Joseph's Health Care, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2 Departments of
Lawson Health Research Institute, Medicine, Microbiology and Immunology, Paediatrics, St Joseph's Health Care, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2 Departments of

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Kelly Summers Lawson Health Research Institute, Medicine, Microbiology and Immunology, Paediatrics, St Joseph's Health Care, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2 Departments of
Lawson Health Research Institute, Medicine, Microbiology and Immunology, Paediatrics, St Joseph's Health Care, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2 Departments of

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David J Hill Lawson Health Research Institute, Medicine, Microbiology and Immunology, Paediatrics, St Joseph's Health Care, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2 Departments of
Lawson Health Research Institute, Medicine, Microbiology and Immunology, Paediatrics, St Joseph's Health Care, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2 Departments of
Lawson Health Research Institute, Medicine, Microbiology and Immunology, Paediatrics, St Joseph's Health Care, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2 Departments of
Lawson Health Research Institute, Medicine, Microbiology and Immunology, Paediatrics, St Joseph's Health Care, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2 Departments of

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Introduction Type 1 diabetes originates with the autoimmune-mediated destruction of pancreatic β-cells, and is characterized by a change in cytokine secretion from a helper T-cell (Th) 2 phenotype with relatively low levels of interferon γ (IFNγ

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Lihong Fu Shanghai National Research Center for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Yixuan Qiu Shanghai National Research Center for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Linyan Shen Shanghai National Research Center for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Department of Endocrinology, East Hospital, Tongji University School of Medicine, Shanghai, China

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Canqi Cui Shanghai National Research Center for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Shuang Wang BGI Genomics, BGI-Shenzhen, Shenzhen, China

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Shujie Wang Shanghai National Research Center for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Yun Xie Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Xinjie Zhao Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China

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Xianfu Gao Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

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Guang Ning Shanghai National Research Center for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Aifang Nie Shanghai National Research Center for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Yanyun Gu Shanghai National Research Center for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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2 diabetes mellitus (T2D) ( Turnbaugh et al . 2006 , Qin et al . 2012 , Ridaura et al . 2013 , Lynch & Pedersen 2016 ). Ablating gut microbiota, as in germ free (GF) mice, improves glucose tolerance and renders mice resistant to diet

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Benjamin J Lamont Department of Medicine (Austin Health), The University of Melbourne, Melbourne, Victoria, Australia

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Sofianos Andrikopoulos Department of Medicine (Austin Health), The University of Melbourne, Melbourne, Victoria, Australia

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approved in many countries for use in patients with type 2 diabetes. A number of others are in late-stage clinical development. All these drugs act to enhance incretin signalling not only in pancreatic β-cells, but also in other pancreatic cells and tissues

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Mugdha V Joglekar
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Vinay M Joglekar Stem Cells and Diabetes Section, Shree Seva Medical Foundation, Lab 10, National Center for Cell Science, Ganeshkhind Road, Pune MH 411007, India

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Sheela V Joglekar Stem Cells and Diabetes Section, Shree Seva Medical Foundation, Lab 10, National Center for Cell Science, Ganeshkhind Road, Pune MH 411007, India

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Anandwardhan A Hardikar
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pancreatic islets are known to retain epigenetic marks of active insulin promoter ( Mutskov et al . 2007 ), such islet-derived cells are believed to be of potential importance for cell replacement therapy in diabetes. Though mouse insulin-producing cells are

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Thomas H Claus Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Clark Q Pan Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Joanne M Buxton Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Ling Yang Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Jennifer C Reynolds Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Nicole Barucci Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Michael Burns Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Astrid A Ortiz Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Steve Roczniak Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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James N Livingston Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Kevin B Clairmont Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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James P Whelan Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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development for the treatment of type 2 diabetes ( Weber 2004 and for review, see Knudsen 2004 ). One frequently observed side-effect of GLP-1, or its analogues, is nausea and vomiting correlating with the inhibition of gastrointestinal (GI) motility ( Buse

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B D Green School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom
School of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK

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N Irwin School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom
School of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK

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V A Gault School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom
School of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK

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C J Bailey School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom
School of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK

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F P M O’Harte School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom
School of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK

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P R Flatt School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom
School of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK

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weight loss ( Turton et al. 1996 , Larsen et al. 2001 ). Consequently, GLP-1 has been put forward as a potential drug candidate for type 2 diabetes mellitus, and GLP-1 analogues are currently undergoing clinical trials ( Holz & Chepurny 2003

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Kaiyuan Yang Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada

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Jonathan Gotzmann Department of Physiology, University of Alberta, Edmonton, Alberta, Canada

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Sharee Kuny Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, Alberta, Canada

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Hui Huang Department of Physiology, University of Alberta, Edmonton, Alberta, Canada

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Yves Sauvé Department of Physiology, University of Alberta, Edmonton, Alberta, Canada
Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, Alberta, Canada

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Catherine B Chan Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
Department of Physiology, University of Alberta, Edmonton, Alberta, Canada

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Introduction Type 2 diabetes (T2D) is a metabolic disorder associated with chronic hyperglycemia and disruptions in carbo­hydrate, lipid, and protein metabolism, resulting from decreased production or altered responsiveness to insulin ( Reaven

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Daniel M Kelly Department of Human Metabolism, Robert Hague Centre for Diabetes and Endocrinology, Medical School, The University of Sheffield, Sheffield S10 2RX, UK

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T Hugh Jones Department of Human Metabolism, Robert Hague Centre for Diabetes and Endocrinology, Medical School, The University of Sheffield, Sheffield S10 2RX, UK
Department of Human Metabolism, Robert Hague Centre for Diabetes and Endocrinology, Medical School, The University of Sheffield, Sheffield S10 2RX, UK

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Introduction There has been an alarming increase, of epidemic proportions, in both obesity and diabetes in the general population with increased cardiovascular risk associated with type 2 diabetes mellitus (T2DM) and/or metabolic syndrome (MetS

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Tao Xie Signal Transduction Section, Metabolic Diseases Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA

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Min Chen Signal Transduction Section, Metabolic Diseases Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA

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Lee S Weinstein Signal Transduction Section, Metabolic Diseases Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA

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Introduction Both type 1 and type 2 diabetes have been associated with pancreatic β-cell dysfunction, with reduced glucose-stimulated insulin secretion and decreased β-cell mass due to impaired β-cell proliferation and survival ( Butler et al

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Risheng Ye
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Min Ni
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Miao Wang
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Shengzhan Luo
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Genyuan Zhu
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Robert H Chow Department of Biochemistry and Molecular Biology, Department of Physiology and Biophysics, USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, California 90089-9176, USA

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Amy S Lee
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. 2005 ). Furthermore, variations within IP3R3 have been identified as a risk factor for type 1 diabetes in humans ( Roach et al . 2006 ). IP3R1 is the most abundant isoform in mouse brain and pancreatic β-cells ( De Smedt et al . 1997 , Lee & Laychock

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