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Thanh Q Dang Department of Biology, Faculty of Science York University, Toronto, Canada

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Nanyoung Yoon Department of Biology, Faculty of Science York University, Toronto, Canada

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Helen Chasiotis Department of Biology, Faculty of Science York University, Toronto, Canada

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Emily C Dunford School of Kinesiology and Health Science, Faculty of Health and Muscle Health Research Center, York University, Toronto, Canada

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Qilong Feng Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, PA, USA

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Pingnian He Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, PA, USA

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Michael C Riddell School of Kinesiology and Health Science, Faculty of Health and Muscle Health Research Center, York University, Toronto, Canada

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Scott P Kelly Department of Biology, Faculty of Science York University, Toronto, Canada

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Gary Sweeney Department of Biology, Faculty of Science York University, Toronto, Canada

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potent effects on restricting endothelial transport ( Felinski & Antonetti 2005 , Witt & Sandoval 2014 ), and they contribute to the development of diabetes at least in part by increasing hepatic glucose production and reducing GLUT4 translocation in

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Ling He Division of Metabolism, Division of Endocrinology, Kennedy Krieger Institute, Departments of Pediatrics, Physiology and Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA

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Shumei Meng Division of Metabolism, Division of Endocrinology, Kennedy Krieger Institute, Departments of Pediatrics, Physiology and Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA

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Emily L Germain-Lee Division of Metabolism, Division of Endocrinology, Kennedy Krieger Institute, Departments of Pediatrics, Physiology and Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA
Division of Metabolism, Division of Endocrinology, Kennedy Krieger Institute, Departments of Pediatrics, Physiology and Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA

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Sally Radovick Division of Metabolism, Division of Endocrinology, Kennedy Krieger Institute, Departments of Pediatrics, Physiology and Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA

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Fredric E Wondisford Division of Metabolism, Division of Endocrinology, Kennedy Krieger Institute, Departments of Pediatrics, Physiology and Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA

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Introduction Diabetes mellitus is increasing in prevalence worldwide due to dietary excesses and sedentary lifestyles. About 25.8 million individuals in the USA have diabetes, accounting for 8.3% of the population. Type 2 diabetes previously was

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Rachel K Meyer School of Nutritional Sciences and Wellness, University of Arizona, Tucson, Arizona, USA

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Frank A Duca School of Animal and Comparative Biomedical Sciences, College of Agricultural and Life Sciences, University of Arizona, Tucson, Arizona, USA
BIO5 Institute, University of Arizona, Tucson, Arizona, USA

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GLP-1R activation ( Baggio et al. 2004 ). Further, oxyntomodulin production is blunted in individuals with type 2 diabetes (T2D) ( Wewer Albrechtsen et al. 2016 ), and treatment with oxyntomodulin is beneficial for glucose homeostasis via the

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Morten Lundh Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Chemical Biology and Therapeutics Program, Broad Institute of Harvard and MIT, Boston, Massachusetts, USA

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Marco Bugliani Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Tina Dahlby Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

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Danny Hung-Chieh Chou Chemical Biology and Therapeutics Program, Broad Institute of Harvard and MIT, Boston, Massachusetts, USA

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Bridget Wagner Chemical Biology and Therapeutics Program, Broad Institute of Harvard and MIT, Boston, Massachusetts, USA

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Seyed Mojtaba Ghiasi Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

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Vincenzo De Tata Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

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Zhifei Chen Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

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Marianne Nissan Lund Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Food Science, University of Copenhagen, Copenhagen, Denmark

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Michael J Davies Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

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Piero Marchetti Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Thomas Mandrup-Poulsen Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

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animal models, and our study clarifies the translational potential of this concept, in that our data in human islets do not support the use of inhibitors selective for the i-proteasome in diabetes. In conclusion, beta cells upregulate immunoproteasome

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Sara S Ellingwood Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, Kentucky, USA

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Alan Cheng Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, Kentucky, USA

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there is no conflict of interest that could be perceived as prejudicing the impartiality of this review. Funding This work was supported in part by the American Diabetes Association (#1-17-IBS-135 to A C). S S E was supported by the National

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Yi Lin Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center (OUHSC), BMSB 662A, PO Box 26901, 940 SL Young Boulevard, Oklahoma City, Oklahoma 73104, USA

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Zhongjie Sun Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center (OUHSC), BMSB 662A, PO Box 26901, 940 SL Young Boulevard, Oklahoma City, Oklahoma 73104, USA

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Introduction It is estimated that diabetes affects about 150 million people worldwide, and this figure is expected to be doubled in the next 20 years ( Zimmet et al . 2001 ). About 90–95% of all North American cases of diabetes are type 2 diabetes

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Paige V Bauer Toronto General Hospital Research Institute and Department of Medicine, UHN, Toronto, ON, Canada
Department of Physiology, University of Toronto, Toronto, ON, Canada

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Frank A Duca Toronto General Hospital Research Institute and Department of Medicine, UHN, Toronto, ON, Canada

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Introduction The incidence of type 2 diabetes has more than doubled since 1980, with over 382 million affected individuals worldwide, in conjunction with an increase in obesity rates and the spread of a western lifestyle ( Scully 2012 ). Given

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Jin-Bong Lee Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon Republic of Korea
Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea

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Sung-Jin Yoon Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea

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Sang-Hyun Lee Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea

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Moo-Seung Lee Department of Biomolecular Science, University of Science and Technology, Daejeon, Republic of Korea
Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea

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Haiyoung Jung Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea
Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea

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Tae-Don Kim Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea
Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea

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Suk Ran Yoon Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea
Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea

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Inpyo Choi Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea
Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea

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Ik-Soo Kim Hanwool Life Sciences, Daejeon, Republic of Korea

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Su Wol Chung School of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, Republic of Korea

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Hee Gu Lee Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea
Department of Biomolecular Science, University of Science and Technology, Daejeon, Republic of Korea

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Jeong-Ki Min Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
Department of Biomolecular Science, University of Science and Technology, Daejeon, Republic of Korea

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Young-Jun Park Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon Republic of Korea
Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea

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-α (TNF-α), which also influence insulin sensitivity ( Hofmann et al . 1994 ). Recently, many reports have examined how the phosphorylation of PPARγ is a crucial factor in modulating adipose tissue function, specifically as it relates to diabetes and

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Tessa J Roseboom Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development, Amsterdam Public Health Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam Reproduction and Development, Amsterdam Public Health Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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babies who were small at birth were at increased risk of developing type 2 diabetes. Hales had found that nutritional interventions during early development affected pancreatic development and glucose tolerance. They hypothesised that poor nutrition in

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Li Ding Department of Physiology and Pathophysiology, Peking University Health Science Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

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Yue Yin Department of Physiology and Pathophysiology, Peking University Health Science Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

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Lingling Han Department of Physiology and Pathophysiology, Peking University Health Science Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

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Yin Li Department of Physiology and Pathophysiology, Peking University Health Science Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

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Jing Zhao Department of Physiology and Pathophysiology, Peking University Health Science Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

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Weizhen Zhang Department of Physiology and Pathophysiology, Peking University Health Science Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, USA

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Brand Glucometer (Roche) with blood collected from the tail vein. Glucose clamp studies Two-hour hyperglycemic clamps were performed in either WT or TN mice fasted for 4 h following the instruction of National Institute of Diabetes and Digestive

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