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Doron Weinstein
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Rive Sarfstein
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Zvi Laron Department of Human Molecular Genetics and Biochemistry, Endocrinology and Diabetes Research Unit, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel

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Haim Werner
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. Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease . Endocrine Reviews 2009 30 586 – 623 . ( doi:10.1210/er.2008-0047 ). 11 Bae VL Jackson-Cook CK Maygarden SJ Plymate SR Chen J Ware JL

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Marie Reeberg Sass 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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Nicolai Jacob Wewer Albrechtsen 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
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark

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Jens Pedersen 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
Department of Endocrinology and Nephrology, Nordsjællands University Hospital, Hillerød, Denmark

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Kristine Juul Hare Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Nis Borbye-Lorenzen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark

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Katalin Kiss Department of Pathology, Rigshospitalet, Copenhagen, Denmark

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

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Filip Krag Knop 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
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Steen Seier Poulsen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Niklas Rye Jørgensen Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Jens Juul 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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Cathrine Ørskov Department of Biomedical Sciences, 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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resorption ( 6 ). Finally, we studied the expression of insulin receptors ( INSR ), insulin-like growth factor 1 receptors ( IGF1R ), and insulin-like growth factor 2 receptors ( IGF2R ) in the parathyroid gland on formalin fixed, paraffin embedded (FFPE

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R C S van Adrichem
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L J Hofland
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R A Feelders
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M C De Martino
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P M van Koetsveld
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C H J van Eijck Department of Internal Medicine, Department of Surgery, Department of Pathology, Sector of Endocrinology, Erasmus MC, ‘s Gravendijkwal 230, Room D-430, 3015 CE Rotterdam, The Netherlands

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R R de Krijger Department of Internal Medicine, Department of Surgery, Department of Pathology, Sector of Endocrinology, Erasmus MC, ‘s Gravendijkwal 230, Room D-430, 3015 CE Rotterdam, The Netherlands

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D M Sprij-Mooij
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J A M J L Janssen
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W W de Herder
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functions in normal tissues and tumors, plays an important role in the pathophysiology of GEP NETs (2) . The IGF system consists of different IGF-related genes: two ligands (IGF1 and IGF2), two IGF receptors (IGF1R and IGF2R), two insulin receptors (IR

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Clemens Kamrath Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany

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Alexander Eckert German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm University, Ulm, Germany

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Birgit Rami-Merhar Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria

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Sebastian Kummer Department of General Pediatrics, Neonatology and Pediatric Cardiology, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany

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Martin Wabitsch Center for Rare Endocrine Diseases, Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Centre, Ulm, Germany

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Katharina Laubner Division of Endocrinology and Diabetology, Department of Medicine II, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

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Florian Kopp Forth Clinical Department of Medicine, Academic Teaching Hospital Augsburg, Augsburg, Germany

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Silvia Müther Center for Pediatric Diabetology, DRK-Kliniken-Berlin Westend, Berlin, Germany

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Steffen Mühldorfer Department for Gastroenterology, Endocrinology and Metabolic Diseases, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Reinhard W Holl German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm University, Ulm, Germany

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both. Primary defects in insulin signaling due to impaired insulin receptors or abnormal signal transduction are very rare disorders leading to diabetes with severe insulin resistance. The spectrum of clinical severity is related to the degree of

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Leanne Hodson Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), Oxford University Hospital Trusts, Oxford, UK

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Fredrik Karpe Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), Oxford University Hospital Trusts, Oxford, UK

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). For the initial step of hepatic insulin extraction to occur, insulin receptors must be present and it is plausible, the total number of receptors available may influence extraction. By measuring insulin receptors on hepatic membranes Arner et al

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Kaisa K Ivaska
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Maikki K Heliövaara Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland

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Pertti Ebeling Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland

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Marco Bucci Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland

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Ville Huovinen Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland
Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland
Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland

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H Kalervo Väänänen
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Pirjo Nuutila Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland
Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland

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Heikki A Koistinen Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland
Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland

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(9, 10) . Clinical observations in patients with types 1 and 2 diabetes mellitus suggest that insulin may act as an anabolic agent in bone and preserve bone mass in humans (11, 12) . Insulin receptors have been detected in osteosarcoma cell lines and

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Xiaohui Qi Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Ping He Shanghai Hospital Link Center, Shanghai Hospital Development Center, Shanghai, China

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Huayan Yao Computer Net Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Huanhuan Sun Wonders Information Co. Ltd, Shanghai, China

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Jiying Qi Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Min Cao Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Bin Cui Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Guang Ning Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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because it is structurally modified ( 20 , 21 ). In addition to activating the insulin receptor cascade response, long-acting insulin analogs can also affect the IGF-1 receptor cascade response ( 22 ). And there is evidence from Alvaro’s study that IGF-1

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Wenjun Long Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

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Tuo Zhou Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

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Xiuping Xuan Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China

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Qiuli Cao Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China

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Zuojie Luo Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China

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Yingfen Qin Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China

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Qin Ning Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

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Xiaoping Luo Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

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Xuemei Xie Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China

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. Insulin signaling was impaired in skeletal muscle of male CG-IUGR To investigate the insulin signaling in skeletal muscle of male CG-IUGR, the protein and mRNA level of insulin receptor (IR)-β and insulin receptor substrate (IRS)-1, two canonical

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Kyoungjune Pak Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea

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Seongho Seo Department of Electronic Engineering, Pai Chai University, Daejeon, Republic of Korea

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Myung Jun Lee Department of Neurology, Pusan National University Hospital, Busan, Republic of Korea

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Keunyoung Kim Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea

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Sunghwan Suh Department of Internal Medicine, Dong-A University College of Medicine, Busan, Republic of Korea

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Hyung-Jun Im Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea

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In Joo Kim Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea

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as well as the brain ( 4 , 5 ). As insulin is released from the pancreas in response to increased glucose levels as a consequence of food intake ( 6 ), it crosses the blood-brain barrier and stimulates insulin receptors ( 7 ). There is growing

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N K Stepto Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia
Australian Institute for Musculoskeletal Science, Victoria University, Melbourne, Victoria, Australia
Medicine-Western Health, Faculty of Medicine, Dentistry and Health Science, Melbourne University, Melbourne, Victoria, Australia

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D Hiam Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia

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M Gibson-Helm Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia

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S Cassar Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia

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C L Harrison Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia

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S K Hutchison Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia

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A E Joham Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia

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B J Canny School of Medicine, University of Tasmania, Hobart, Tasmania, Australia

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A Moreno-Asso Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
Australian Institute for Musculoskeletal Science, Victoria University, Melbourne, Victoria, Australia

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B J Strauss Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
Division of Diabetes, Endocrinology & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK

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N Hatzirodos The Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, Australia

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R J Rodgers The Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, Australia

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H J Teede Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia
Diabetes and Endocrine Units, Monash Health, Clayton, Victoria, Australia

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, 18 ), with reduced activation of key signalling proteins such as insulin receptor substrate (IRS)1/2, protein kinase B (PKB)/Akt and its downstream substrate Akt substrate 160KDa (AS160) ( 17 , 18 , 19 ). While similar defects in insulin stimulated

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