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Richard W Nelson Department of Medicine and Epidemiology, Clinic for Small Animal Internal Medicine, School of Veterinary Medicine, University of California, Davis, California 95616, USA

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Claudia E Reusch Department of Medicine and Epidemiology, Clinic for Small Animal Internal Medicine, School of Veterinary Medicine, University of California, Davis, California 95616, USA

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Introduction Diabetes mellitus is a common disorder in dogs and cats, with a reported hospital prevalence rate of ∼0.4–1.2%. Classic clinical signs of diabetes include polyuria, polydipsia, polyphagia, and weight loss. Clinical signs do not develop

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Johan G Eriksson Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Folkhälsan Research Center, University of Helsinki, Helsinki, Finland
Department of Obstetrics and Gynecology, National University of Singapore, Yong Loo Lin School of Medicine, Singapore, Singapore

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Type 2 diabetes Type 2 diabetes (T2D) is a major, rapidly increasing global public health challenge. The number of adults with diabetes is estimated to have increased from 108 to 422 million between 1980 and 2014 making it one of the fastest

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Che-Pei Kung Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA

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Maureen E Murphy Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA

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diabetes. Structure and function of the p53 tumor-suppressor protein p53 protein is made of 393 amino acids and uses a zinc-coordinated DNA-binding domain to bind in a sequence-specific manner to DNA consensus elements that contain two copies of the

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S J Brandt Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
German Center for Diabetes Research (DZD), Neuherberg, Germany

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M Kleinert Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
German Center for Diabetes Research (DZD), Neuherberg, Germany

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M H Tschöp Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
German Center for Diabetes Research (DZD), Neuherberg, Germany
Division of Metabolic Diseases, Technische Universität, Munich, Germany

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T D Müller Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
German Center for Diabetes Research (DZD), Neuherberg, Germany

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obesity are associated with a number of comorbidities, most importantly type 2 diabetes (T2DM), cardiovascular disease, hypertension, dyslipidemia and several kinds of cancer, predominantly gastrointestinal (GI). In 2015, around 4 million deaths were

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Jasleen Kaur Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA

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Elizabeth R Seaquist Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA

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understanding of the physiology of glucagon, its potential role in the causation of diabetes, and its synergistic effects with other gut hormones in regulating metabolism. In this review article, we aim to summarize the known effects of glucagon and its

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Robin Kristófi 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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Introduction Metformin is a biguanide drug that is widely prescribed as an oral antihyperglycaemic agent internationally and is recommended as the initial drug of choice for type 2 diabetes (T2D) according to recent joint European

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Brittany M Duggan Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, and Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada

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Daniel M Marko Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, and Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada

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Raveen Muzaffar Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, and Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada

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Darryl Y Chan Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, and Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada

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Jonathan D Schertzer Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, and Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada

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, inflammatory bowel disease, peritonitis, multiple sclerosis, pulmonary fibrosis, and type 1 and type 2 diabetes (T1D, T2D) ( Patterson et al. 2014 ). Several of these agents have already been approved for use in several non-malignant conditions including

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John N Stabley Department of Applied Physiology and Kinesiology, Department of Kinesiology and Applied Physiology, Department of Kinesiology, Department of Nutrition, University of Florida, Gainesville, Florida 32611, USA

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Rhonda D Prisby Department of Applied Physiology and Kinesiology, Department of Kinesiology and Applied Physiology, Department of Kinesiology, Department of Nutrition, University of Florida, Gainesville, Florida 32611, USA

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Bradley J Behnke Department of Applied Physiology and Kinesiology, Department of Kinesiology and Applied Physiology, Department of Kinesiology, Department of Nutrition, University of Florida, Gainesville, Florida 32611, USA
Department of Applied Physiology and Kinesiology, Department of Kinesiology and Applied Physiology, Department of Kinesiology, Department of Nutrition, University of Florida, Gainesville, Florida 32611, USA

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Michael D Delp Department of Applied Physiology and Kinesiology, Department of Kinesiology and Applied Physiology, Department of Kinesiology, Department of Nutrition, University of Florida, Gainesville, Florida 32611, USA
Department of Applied Physiology and Kinesiology, Department of Kinesiology and Applied Physiology, Department of Kinesiology, Department of Nutrition, University of Florida, Gainesville, Florida 32611, USA

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Introduction The increase in fracture risk observed among patients with type 2 diabetes mellitus (T2DM) has been suggested to be associated with corollaries of the disease, such as peripheral neuropathy, decreased physical fitness, vision loss, and

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Rui Gao Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK

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Samuel Acreman Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK
Department of Physiology, Institute of Neuroscience and Physiology, Metabolic Research Unit, University of Gothenburg, Göteborg, Sweden

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Jinfang Ma Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK

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Fernando Abdulkader Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil

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Anna Wendt Department of Clinical Sciences Malmö, Islet Cell Exocytosis, Lund University Diabetes Centre, Lund University, Malmö, Sweden

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Quan Zhang Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK
CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal

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hyperglycaemia ( Göke 2008 ). This secretory pattern becomes defective in diabetes and leads to glycaemic volatility: failure to secrete glucagon at low glucose contributes to the occurrence of hypoglycaemia ( Cryer & Gerich 1985 ), while hyperglucagonemia at

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Hao Wu Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China
The ‘973’ National Basic Research Program of China, Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of China

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Junduo Wu Department of Cardiology, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China

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Shengzhu Zhou Department of Anesthesiology, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China

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Wenlin Huang School of Science and Technology, Georgia Gwinnett College, Lawrenceville, Georgia, USA

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Ying Li Department of Dermatology, Affiliated Hospital of Beihua University, Jilin, Jilin, People’s Republic of China

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Huan Zhang Operating Theatre, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China

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Junnan Wang Department of Cardiology, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China

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Ye Jia Department of Nephrology, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China

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Introduction Macrovascular complications develop in >50% of the diabetic patients and result in high mortality ( King & Wakasaki 1999 , Forbes et al . 2004 ). Given the dramatic increase in the prevalence of diabetes mellitus (DM

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