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Akiko Mizokami OBT Research Center, Faculty of Dental Science, Kyushu University, Fukuoka, Japan

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Satoru Mukai OBT Research Center, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan

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Jing Gao Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan

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Tomoyo Kawakubo-Yasukochi Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan

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Takahito Otani Division of Functional Structure, Department of Morphological Biology, School of Dental Medicine, Fukuoka Dental College, Fukuoka, Japan

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Hiroshi Takeuchi Division of Applied Pharmacology, Kyushu Dental University, Kitakyushu, Japan

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Eijiro Jimi OBT Research Center, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan

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Masato Hirata Oral Medicine Research Center, School of Dental Medicine, Fukuoka Dental College, Fukuoka, Japan

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et al. 2014 ) or indirectly through stimulation of the secretion of glucagon-like peptide-1 (GLP-1) from intestinal endocrine cells ( Mizokami et al. 2013 , 2014 ). GLP-1 is a member of the incretin family of hormones that are secreted from

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Xianxian Huang Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, China

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Jing Liu Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, China

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Guangquan Peng Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, China

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Mingyue Lu Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, China

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Zhongbo Zhou School of Pharmacy, Youjiang Medical University for Nationalities, Baise, Guangxi, China

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Neng Jiang Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, China

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Zhiming Yan Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, China

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, glucagon-like peptide 1; GIP, glucose-dependent insulinotropic peptide; GLP-1R, glucagon-like peptide 1 receptor; GIPR, glucose-dependent insulinotropic peptide receptor; GLP-1RA, glucagon-like peptide 1 receptor agonist; T2DM, type 2 diabetes mellitus

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Jennifer S ten Kulve Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

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Dick J Veltman Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands

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Liselotte van Bloemendaal Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

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Paul F C Groot Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands

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Henricus G Ruhé Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands

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Frederik Barkhof Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands

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Michaela Diamant Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

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Richard G Ijzerman Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

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, Cummings 2013 ), except for glucagon-like peptide-1 (GLP1). GLP1 is a gut-derived hormone, mainly known for its glucose-lowering effects ( Kreymann et al. 1987 , Mojsov et al. 1987 ); however, numerous preclinical and clinical studies have shown that

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Wenjuan Liu Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China

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Harry Kevin Lau Division of Endocrinology and Metabolism, The Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada

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Dong Ok Son Division of Endocrinology and Metabolism, The Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada

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Tianru Jin Department of Physiology, University of Toronto, Toronto, Ontario, Canada
Division of Advanced Diagnostics, Toronto General Research Institutes, University Health Network, Toronto, Ontario, Canada
Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada

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Yehong Yang Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China

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Zhaoyun Zhang Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China

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Yiming Li Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China

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Gerald J Prud’homme Department of Laboratory Medicine and Pathobiology, Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada

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Qinghua Wang Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China

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the β-cell mass and provide improved treatments for T1D and T2D subjects. Glucagon-like peptide-1 (GLP-1) is an incretin hormone released from gastrointestinal L cells in response to food ingestion, and has been currently used for the treatment of T2

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M-J Kim Departments of Physiology and
Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
Department of Biochemistry, College of Medicine, Korea University, Seoul 136-701, Korea
Department of Internal Medicine, School of Medicine, Hallym University, Seoul 150-030, Korea
Department of Food Science and Nutrition, The Catholic University of Korea, Puchon City 420-743, Korea

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J-H Kang Departments of Physiology and
Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
Department of Biochemistry, College of Medicine, Korea University, Seoul 136-701, Korea
Department of Internal Medicine, School of Medicine, Hallym University, Seoul 150-030, Korea
Department of Food Science and Nutrition, The Catholic University of Korea, Puchon City 420-743, Korea

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Y G Park Departments of Physiology and
Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
Department of Biochemistry, College of Medicine, Korea University, Seoul 136-701, Korea
Department of Internal Medicine, School of Medicine, Hallym University, Seoul 150-030, Korea
Department of Food Science and Nutrition, The Catholic University of Korea, Puchon City 420-743, Korea

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G R Ryu Departments of Physiology and
Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
Department of Biochemistry, College of Medicine, Korea University, Seoul 136-701, Korea
Department of Internal Medicine, School of Medicine, Hallym University, Seoul 150-030, Korea
Department of Food Science and Nutrition, The Catholic University of Korea, Puchon City 420-743, Korea

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S H Ko Departments of Physiology and
Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
Department of Biochemistry, College of Medicine, Korea University, Seoul 136-701, Korea
Department of Internal Medicine, School of Medicine, Hallym University, Seoul 150-030, Korea
Department of Food Science and Nutrition, The Catholic University of Korea, Puchon City 420-743, Korea

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I-K Jeong Departments of Physiology and
Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
Department of Biochemistry, College of Medicine, Korea University, Seoul 136-701, Korea
Department of Internal Medicine, School of Medicine, Hallym University, Seoul 150-030, Korea
Department of Food Science and Nutrition, The Catholic University of Korea, Puchon City 420-743, Korea

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K-H Koh Departments of Physiology and
Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
Department of Biochemistry, College of Medicine, Korea University, Seoul 136-701, Korea
Department of Internal Medicine, School of Medicine, Hallym University, Seoul 150-030, Korea
Department of Food Science and Nutrition, The Catholic University of Korea, Puchon City 420-743, Korea

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D-J Rhie Departments of Physiology and
Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
Department of Biochemistry, College of Medicine, Korea University, Seoul 136-701, Korea
Department of Internal Medicine, School of Medicine, Hallym University, Seoul 150-030, Korea
Department of Food Science and Nutrition, The Catholic University of Korea, Puchon City 420-743, Korea

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S H Yoon Departments of Physiology and
Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
Department of Biochemistry, College of Medicine, Korea University, Seoul 136-701, Korea
Department of Internal Medicine, School of Medicine, Hallym University, Seoul 150-030, Korea
Department of Food Science and Nutrition, The Catholic University of Korea, Puchon City 420-743, Korea

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S J Hahn Departments of Physiology and
Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
Department of Biochemistry, College of Medicine, Korea University, Seoul 136-701, Korea
Department of Internal Medicine, School of Medicine, Hallym University, Seoul 150-030, Korea
Department of Food Science and Nutrition, The Catholic University of Korea, Puchon City 420-743, Korea

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M-S Kim Departments of Physiology and
Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
Department of Biochemistry, College of Medicine, Korea University, Seoul 136-701, Korea
Department of Internal Medicine, School of Medicine, Hallym University, Seoul 150-030, Korea
Department of Food Science and Nutrition, The Catholic University of Korea, Puchon City 420-743, Korea

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Y-H Jo Departments of Physiology and
Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
Department of Biochemistry, College of Medicine, Korea University, Seoul 136-701, Korea
Department of Internal Medicine, School of Medicine, Hallym University, Seoul 150-030, Korea
Department of Food Science and Nutrition, The Catholic University of Korea, Puchon City 420-743, Korea

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Introduction Glucagon-like peptide-1 (GLP-1) has been of much interest due to its β-cell-proliferating effect and role as an incretin hormone in synergizing with glucose to enhance insulin release ( Ørskov 1992 , Egan et al. 2003

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Mohamed Lotfy Department of Biology, School of Forensic and Investigative Sciences, Hormones Department, School of Pharmacy and Biomedical Sciences, Anatomy, Medical Microbiology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates
Department of Biology, School of Forensic and Investigative Sciences, Hormones Department, School of Pharmacy and Biomedical Sciences, Anatomy, Medical Microbiology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates
Department of Biology, School of Forensic and Investigative Sciences, Hormones Department, School of Pharmacy and Biomedical Sciences, Anatomy, Medical Microbiology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates

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Jaipaul Singh Department of Biology, School of Forensic and Investigative Sciences, Hormones Department, School of Pharmacy and Biomedical Sciences, Anatomy, Medical Microbiology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates
Department of Biology, School of Forensic and Investigative Sciences, Hormones Department, School of Pharmacy and Biomedical Sciences, Anatomy, Medical Microbiology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates

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Hameed Rashed Department of Biology, School of Forensic and Investigative Sciences, Hormones Department, School of Pharmacy and Biomedical Sciences, Anatomy, Medical Microbiology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates

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Saeed Tariq Department of Biology, School of Forensic and Investigative Sciences, Hormones Department, School of Pharmacy and Biomedical Sciences, Anatomy, Medical Microbiology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates

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Erika Zilahi Department of Biology, School of Forensic and Investigative Sciences, Hormones Department, School of Pharmacy and Biomedical Sciences, Anatomy, Medical Microbiology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates

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Ernest Adeghate Department of Biology, School of Forensic and Investigative Sciences, Hormones Department, School of Pharmacy and Biomedical Sciences, Anatomy, Medical Microbiology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates

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endocrine and an exocrine system with much interaction between the two parts ( Shetzline & Liddle 2002 ). The GI tract secretes a number of hormones including glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP1; Drucker 2003 b

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Christian Hölscher Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK

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Introduction The main hallmark of type 2 diabetes mellitus (T2DM) is insulin desensitisation. The discovery that the incretin hormone glucagon-like peptide 1 (GLP-1) facilitates insulin release during episodes of hyperglycaemia and has several

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Jonathan D Douros Novo Nordisk Research Center Indianapolis, Indianapolis, Indiana, USA

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Jacek Mokrosinski Novo Nordisk Research Center Indianapolis, Indianapolis, Indiana, USA

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Brian Finan Novo Nordisk Research Center Indianapolis, Indianapolis, Indiana, USA

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disadvantageous regulatory mechanisms in a cell-targeted, pathophysiology-specific manner. This review aims to outline the current understanding of signaling bias at the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) in three broad categories: (i) ligand

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Zhengu Liu Laboratory of Molecular Endocrinology, Their 306, Massachusetts General Hospital, Boston, Massachusetts 02114, USA

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Violeta Stanojevic Laboratory of Molecular Endocrinology, Their 306, Massachusetts General Hospital, Boston, Massachusetts 02114, USA

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Luke J Brindamour Laboratory of Molecular Endocrinology, Their 306, Massachusetts General Hospital, Boston, Massachusetts 02114, USA

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Joel F Habener Laboratory of Molecular Endocrinology, Their 306, Massachusetts General Hospital, Boston, Massachusetts 02114, USA

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of glucagon-like peptide-1 (GLP1; Tomas & Habener 2010 ) enters glucolipotoxic-stressed INS-1 β-cells and inhibits stress-induced apoptosis. We showed earlier that the C-terminal nonapeptide, GLP1(28–36)amide, derived from GLP1 enters insulin

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Yoon Sin Oh Lee Gil Ya Cancer and Diabetes Institute, Department of Endocrinology and Metabolism, Howard Hughes Medical Institute, Gachon Medical Research Institute, Department of Rehabilitation Medicine, College of Pharmacy, Gachon University, 7-45 Songdo‐dong, Yeonsu‐ku, Incheon, Korea
Lee Gil Ya Cancer and Diabetes Institute, Department of Endocrinology and Metabolism, Howard Hughes Medical Institute, Gachon Medical Research Institute, Department of Rehabilitation Medicine, College of Pharmacy, Gachon University, 7-45 Songdo‐dong, Yeonsu‐ku, Incheon, Korea

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Youn-Jung Lee Lee Gil Ya Cancer and Diabetes Institute, Department of Endocrinology and Metabolism, Howard Hughes Medical Institute, Gachon Medical Research Institute, Department of Rehabilitation Medicine, College of Pharmacy, Gachon University, 7-45 Songdo‐dong, Yeonsu‐ku, Incheon, Korea

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Yup Kang Lee Gil Ya Cancer and Diabetes Institute, Department of Endocrinology and Metabolism, Howard Hughes Medical Institute, Gachon Medical Research Institute, Department of Rehabilitation Medicine, College of Pharmacy, Gachon University, 7-45 Songdo‐dong, Yeonsu‐ku, Incheon, Korea

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Jaeseok Han Lee Gil Ya Cancer and Diabetes Institute, Department of Endocrinology and Metabolism, Howard Hughes Medical Institute, Gachon Medical Research Institute, Department of Rehabilitation Medicine, College of Pharmacy, Gachon University, 7-45 Songdo‐dong, Yeonsu‐ku, Incheon, Korea

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Oh-Kyung Lim Lee Gil Ya Cancer and Diabetes Institute, Department of Endocrinology and Metabolism, Howard Hughes Medical Institute, Gachon Medical Research Institute, Department of Rehabilitation Medicine, College of Pharmacy, Gachon University, 7-45 Songdo‐dong, Yeonsu‐ku, Incheon, Korea

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Hee-Sook Jun Lee Gil Ya Cancer and Diabetes Institute, Department of Endocrinology and Metabolism, Howard Hughes Medical Institute, Gachon Medical Research Institute, Department of Rehabilitation Medicine, College of Pharmacy, Gachon University, 7-45 Songdo‐dong, Yeonsu‐ku, Incheon, Korea
Lee Gil Ya Cancer and Diabetes Institute, Department of Endocrinology and Metabolism, Howard Hughes Medical Institute, Gachon Medical Research Institute, Department of Rehabilitation Medicine, College of Pharmacy, Gachon University, 7-45 Songdo‐dong, Yeonsu‐ku, Incheon, Korea

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-cells and diabetes mellitus . Experimental Biology and Medicine 228 1213 – 1217 . Cunha DA Ladriere L Ortis F Igoillo-Esteve M Gurzov EN Lupi R Marchetti P Eizirik DL Cnop M 2009 Glucagon-like peptide-1 agonists protect pancreatic

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