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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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-resistant mice is associated with increased islet GLP1 receptor (GLP1R) protein levels. We then examined the potential to improve islet function and glucose tolerance in glucose-intolerant insulin-resistant mice through GPR119 activation by administering a

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Shaomin Shi Division of Nephrology, The First Affiliated Hospital of Yangtze University, Jingzhou, China

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Xinghua Chen Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China

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Wen Yu Department of Immunology, School of Medicine, Yangtze University, Jingzhou, China

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Xiaolan Ke Division of Nephrology, The First Affiliated Hospital of Yangtze University, Jingzhou, China

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Tean Ma Division of Nephrology, The First Affiliated Hospital of Yangtze University, Jingzhou, China

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(GLP-1R). GLP-1R is expressed in islet β-cells and several extrapancreatic tissues, including the small inlet arteries, proximal tubules, and collecting ducts of the kidney ( 12 , 13 ). GLP-1R activity is significantly reduced in chronic kidney disease

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Shenghe Luo College of Pharmacy, Yanbian University, Yanji, China

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Yunhui Zuo Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, China
Department of Cardiology, Yanbian University Hospital, Yanji, China

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Xiaotian Cui Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, China

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Meiping Zhang Department of Cardiology, Yanbian University Hospital, Yanji, China

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Honghua Jin Department of Pharmacy, Yanbian University Hospital, Yanji, China

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Lan Hong Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, China

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Introduction Glucagon-like peptide 1 (GLP-1) is one of the components of incretin, which can regulate the metabolism of the body and has a wide range of pharmacological effects ( 1 , 2 ). GLP-1R agonists like as liraglutide are currently

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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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Agnieszka Kosowska Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Enrique Gallego-Colon Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Wojciech Garczorz Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Agnieszka Kłych-Ratuszny Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Mohammad Reza F Aghdam Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Michał Woz´niak Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Andrzej Witek Department of Gynaecology and Obstetrics, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Agnieszka Wróblewska-Czech Department of Gynaecology and Obstetrics, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Anna Cygal Department of Gynaecology and Obstetrics, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Jerzy Wojnar Department of Internal Medicine and Oncological Chemotherapy, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Tomasz Francuz Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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mechanism of action of incretin mimetic drugs is through the binding to glucagon-like peptide-1 receptor (GLP-1R) in pancreatic beta cells stimulating insulin secretion. The two most important natural incretin hormones are glucagon-like peptide-1 (GLP-1) and

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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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Christine Rode Andreasen Steno Diabetes Center Copenhagen, Gentofte, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Andreas Andersen Steno Diabetes Center Copenhagen, Gentofte, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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

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. Thus, only 10% of the native GLP-1 released from the enteroendocrine L cells reaches the systemic circulation ( 1 ). Activation of the GLP-1 receptor (GLP-1R) on the beta-cell enhances glucose-dependent secretion of insulin, thereby improving beta

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Marie Oertel Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany

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Christian G Ziegler Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany
Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Dresden, Germany

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Michael Kohlhaas Comprehensive Heart Failure Center, Würzburg, Germany

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Alexander Nickel Comprehensive Heart Failure Center, Würzburg, Germany

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Simon Kloock Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany

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Christoph Maack Comprehensive Heart Failure Center, Würzburg, Germany

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Vasco Sequeira Comprehensive Heart Failure Center, Würzburg, Germany

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Martin Fassnacht Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany

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Ulrich Dischinger Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany
Comprehensive Heart Failure Center, Würzburg, Germany

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, 20 ). Long-acting GLP-1 receptor (GLP-1-R) agonists, e.g. semaglutide, are already in clinical use for the treatment of obesity. In adults with overweight or obesity and without diabetes mellitus, semaglutide leads to a mean weight loss of about 10

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Riying Liang Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China
Department of Ultrasound, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

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Meijun Wang Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China

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Chang Fu Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China

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Hua Liang Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China

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Hongrong Deng Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China

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Ying Tan Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China

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Fen Xu Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China

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Mengyin Cai Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China

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group ( 35 ). Recent studies have shown that GLP-1R agonists exerted the reno-protective anti-inflammatory, anti-fibrosis, and anti-apoptosis effects, as well as reduction of renin-angiotensin-aldosterone system (RASS) ( 13 , 36 , 37 , 38 ). In the

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Jukka Koffert Department of Gastroenterology, Turunmaa Hospital, Turku, Finland
Turku PET Centre, University of Turku, Turku, Finland

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Henri Honka Turku PET Centre, University of Turku, Turku, Finland

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Jarmo Teuho Department of Gastroenterology, Turunmaa Hospital, Turku, Finland

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Saila Kauhanen Division of Digestive Surgery and Urology, Turku University Hospital, Turku, Finland

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Saija Hurme Institute of Biostatistics, University of Turku, Turku, Finland

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Riitta Parkkola Turku PET Centre, University of Turku, Turku, Finland
Department of Radiology, University of Turku and Turku University Hospital, Turku, Finland

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Vesa Oikonen Turku PET Centre, University of Turku, Turku, Finland

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Andrea Mari Institute of Neuroscience, National Research Council, Padua, Italy

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Andreas Lindqvist Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden

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Nils Wierup Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden

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Leif Groop Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden

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Pirjo Nuutila Turku PET Centre, University of Turku, Turku, Finland
Department of Endocrinology, Turku University Hospital, Turku, Finland

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) confirming the glucose dependency of GIP-secretion. However, the same relationship was not observed between increase in glucose and GLP-1 ( r P  = 0.129, P  = 0.722), even though GLP-1 (iAUC) but not GIP response was positively correlated with glucose

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