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Giuseppe Lisco Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare, Bari, Italy

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Anna De Tullio Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare, Bari, Italy

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Olga Disoteo Diabetology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy

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Giuseppina Piazzolla Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare, Bari, Italy

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Edoardo Guastamacchia Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare, Bari, Italy

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Carlo Sabbà Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare, Bari, Italy

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Vincenzo De Geronimo Unit of Endocrinology, Policlinico Morgagni CCD, Catania, Italy

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Enrico Papini Department of Endocrinology and Metabolism, Regina Apostolorum Hospital, Rome, Italy

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Vincenzo Triggiani Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare, Bari, Italy

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evaluate long-term effects ( 17 , 18 , 19 ). The incretin system and thyroid cancer A pivotal study found that the dipeptidyl peptidase type IV (DPP-IV), also known as cluster differentiation 26 (CD26), was expressed widely on the cell surface of

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Amalie R Lanng Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Lærke S Gasbjerg Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Natasha C Bergmann Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Sigrid Bergmann Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Mads M Helsted Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Matthew P Gillum Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Bolette Hartmann Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Jens J Holst Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Tina Vilsbøll Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Steno Diabetes Center Copenhagen, Gentofte, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Filip K Knop Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Gentofte, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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). Likewise, the effect of alcohol on the secretion of the gut-derived insulinotropic incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) remains unclear ( 6 , 11 , 12 ). Recently, alcohol was shown to

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Giovanni Fanni Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden

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Petros Katsogiannos Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden

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Bipasha Nandi Jui Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden

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Magnus Sundbom Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

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Susanne Hetty Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden

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Maria J Pereira Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden

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Jan W Eriksson Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden

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metabolic shift is partly independent of weight loss, and the underlying mechanisms are not completely understood ( 3 , 4 , 5 , 6 ). Shortly after RYGB, a greater incretin response occurs post-prandially, which enhances insulin secretion, reduces food

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Lizhi Zhang Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
Department of Endocrinology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Jinwei He Department of Osteoporosis and Bone Disease, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

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Xiang Sun Shanghai Institute of Technology, Shanghai, China

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Dongyue Pang Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

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Jingjing Hu Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

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Bo Feng Department of Endocrinology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Population in Beijing, China) for GIPR SNP rs10423928 using second-stage HapMap data ( ftp://ftp.ncbi.nlm.nih.gov/hapmap/ ). Both GLP-1 and GIP are incretins. Previously, we demonstrated a correlation between GLP-1 receptor gene ( GLP-1R ) polymorphisms and

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L Ahlkvist
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K Brown Department of Clinical Sciences, GlaxoSmithKline, Biomedical Center, C11, Lund University, SE 22184 Lund, Sweden

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B Ahrén
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contribute to the upregulated β-cell function in insulin resistance, such as signals generated from nutrient metabolism, hormones, and cytokines (2) . We previously suggested that the incretin hormones may also contribute by demonstrating in model

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Svjatoslavs Kistkins Pauls Stradiņš Clinical University Hospital, Riga, Latvia

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Othmar Moser Division of Exercise Physiology and Metabolism, Institute of Sport Science, University of Bayreuth, Bayreuth, Germany

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Vitālijs Ankudovičs Pauls Stradiņš Clinical University Hospital, Riga, Latvia

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Dmitrijs Blizņuks Institute of Smart Computing Technologies, Riga Technical University, Riga, Latvia

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Timurs Mihailovs Institute of Smart Computing Technologies, Riga Technical University, Riga, Latvia

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Sergejs Lobanovs Pauls Stradiņš Clinical University Hospital, Riga, Latvia

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Harald Sourij Trials Unit for Interdisciplinary Metabolic Medicine, Division of Endocrinology and Diabetolgoy, Medical University of Graz, Graz, Austria

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Andreas F H Pfeiffer Department of Endocrinology and Metabolic Medicine, Campus Benjamin Franklin, Charité University Medicine, Hindenburgdamm, Berlin, Germany

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Valdis Pīrāgs Pauls Stradiņš Clinical University Hospital, Riga, Latvia
Faculty of Medicine, University of Latvia, Riga, Latvia

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perspectives in the combinatory use of incretin-based therapies in diabesity and physiological nature of hormonal crosstalk The primary objective of treating diabetes in particular novel pharmacological options leading to significant weight loss is to enhance

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Annieke C G van Baar Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands

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Andrei Prodan Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands

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Camilla D Wahlgren Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark

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Steen S Poulsen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Filip K Knop Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Albert K Groen Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
Department of Laboratory Medicine, University of Groningen, University Medical Center, Groningen, the Netherlands

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Jacques J Bergman Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands

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Max Nieuwdorp Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
Department of Internal Medicine, VUMC Free University, Amsterdam, the Netherlands
Wallenberg Laboratory, Sahlgrenska Hospital, University of Gothenburg, Gothenburg, Sweden

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Evgeni Levin Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
Horaizon BV, Delft, the Netherlands

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, metabolic syndrome (MetS) and type 2 diabetes ( 1 ). The gut incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), produced by enteroendocrine L cells and K cells, respectively, are intimately involved in

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Jothydev Kesavadev Jothydev’s Diabetes Research Centre, Trivandrum, Kerala, India

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Pradeep Babu Sadasivan Pillai Jothydev’s Diabetes Research Centre, Trivandrum, Kerala, India

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Arun Shankar Jothydev’s Diabetes Research Centre, Trivandrum, Kerala, India

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Gopika Krishnan Jothydev’s Diabetes Research Centre, Trivandrum, Kerala, India

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Sunitha Jothydev Jothydev’s Diabetes Research Centre, Trivandrum, Kerala, India

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, many patients will eventually require to be shifted to another class of oral antidiabetic agents or insulin therapy ( 2 , 3 ). DPP-4 inhibitors are a class of oral antidiabetic drugs which enhance the function of endogenous incretin and help with

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Dorte Glintborg Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark

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Hanne Mumm Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark

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Jens Juul Holst Department of Biomedical Sciences and NNF Centre for Basic Metabolic Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

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Marianne Andersen Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark

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). Incretin hormones are released after meal ingestion and account for up to 70% of postprandial insulin secretion ( 3 ). Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide are the most important incretin hormones. GLP-1 secretion is impaired

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Jeppe Skov Department of Endocrinology and Internal Medicine, Novo Nordisk A/S, NNF center for Basic Metabolic Research, Department of Clinical Biochemistry, Department of Clinical Physiology and Molecular Imaging, Department of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark
Department of Endocrinology and Internal Medicine, Novo Nordisk A/S, NNF center for Basic Metabolic Research, Department of Clinical Biochemistry, Department of Clinical Physiology and Molecular Imaging, Department of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark

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Jens Juul Holst Department of Endocrinology and Internal Medicine, Novo Nordisk A/S, NNF center for Basic Metabolic Research, Department of Clinical Biochemistry, Department of Clinical Physiology and Molecular Imaging, Department of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark

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Jens Peter Gøtze Department of Endocrinology and Internal Medicine, Novo Nordisk A/S, NNF center for Basic Metabolic Research, Department of Clinical Biochemistry, Department of Clinical Physiology and Molecular Imaging, Department of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark

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Jørgen Frøkiær Department of Endocrinology and Internal Medicine, Novo Nordisk A/S, NNF center for Basic Metabolic Research, Department of Clinical Biochemistry, Department of Clinical Physiology and Molecular Imaging, Department of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark
Department of Endocrinology and Internal Medicine, Novo Nordisk A/S, NNF center for Basic Metabolic Research, Department of Clinical Biochemistry, Department of Clinical Physiology and Molecular Imaging, Department of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark

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Jens Sandahl Christiansen Department of Endocrinology and Internal Medicine, Novo Nordisk A/S, NNF center for Basic Metabolic Research, Department of Clinical Biochemistry, Department of Clinical Physiology and Molecular Imaging, Department of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark

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Introduction Glucagon-like peptide-1 (GLP1) is a gut-derived incretin hormone with multiple actions in addition to control of glucose homeostasis (1) . Synthetic GLP1 receptor (GLP1R) agonists lower blood pressure in patients with type 2 diabetes

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