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Manuel Gado Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany

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Eva Tsaousidou Sabri Ülker Center for Metabolic Research, Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA

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Stefan R Bornstein Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
Diabetes and Nutritional Sciences, King's College London, London, UK

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Nikolaos Perakakis Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany

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Introduction: pathogenesis of insulin resistance Insulin resistance is defined as the inadequate response of tissues, such as adipose tissue, skeletal muscle, central nervous system, and liver, to insulin. Insulin resistance and impaired

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

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

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

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

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extraction from food ( Bäckhed et al. 2007 ). The gut microbiota can also influence blood glucose. Lower bacterial diversity correlates with insulin resistance and higher adiposity (reviewed in Zhu & Goodarzi 2020 ). Type 2 diabetes (T2D) is associated

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Muraly Puttabyatappa Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA

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Robert M Sargis Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA

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Vasantha Padmanabhan Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA

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Introduction Insulin resistance is a characteristic feature of many metabolic disorders, including the metabolic syndrome, type 2 diabetes mellitus (T2DM), obesity, non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS

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Kok Lim Kua Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

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Shanming Hu Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

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Chunlin Wang Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

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Jianrong Yao Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

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Diana Dang Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

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Alexander B Sawatzke Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

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Jeffrey L Segar Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

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Kai Wang Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA

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Andrew W Norris Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, USA

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Introduction Offspring born from pregnancy complicated by diabetes have a lifelong increased risk of insulin resistance. In humans, such offspring have a 4- to 8-fold higher risk, beyond genetic risk, to develop type 2 diabetes, metabolic

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Amanda J Genders Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Jujiao Kuang Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Evelyn C Marin Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Nicholas J Saner Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Javier Botella Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Macsue Jacques Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Glenn K McConell Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Victor A Andrade-Souza Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Javier Chagolla Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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David J Bishop Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia

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Introduction Patients with insulin resistance have been reported to have decreased skeletal muscle mitochondrial content ( Kelley et al. 2002 , Ritov et al. 2005 , Chomentowski et al. 2011 ) and reductions in skeletal muscle

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Jiean Xu State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Qiuhua Yang State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Xiaoyu Zhang State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Zhiping Liu State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Yapeng Cao State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Lina Wang State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Yaqi Zhou State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Xianqiu Zeng State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Qian Ma State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Yiming Xu Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China

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Yong Wang Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China

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Lei Huang Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, China

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Zhen Han Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, China

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Tao Wang Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, China

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David Stepp Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Zsolt Bagi Department of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Chaodong Wu Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Mei Hong State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China

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Yuqing Huo Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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resistance-associated metabolic perturbations. Accumulating evidence highlights a critical role for adenosine signaling in the development of insulin resistance ( Antonioli et al. 2015 , Pardo et al. 2017 ). Adenosine signaling is also closely

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Gencer Sancar German Center for Diabetes Research, Neuherberg, Germany
Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany
Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany

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Andreas L Birkenfeld German Center for Diabetes Research, Neuherberg, Germany
Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany
Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany

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metabolic disturbances is insulin resistance, which is a condition in which the body's cells become resistant to the effects of insulin, leading to impaired glucose and lipid homeostasis. Adipose tissue dysfunction plays a crucial role in the development of

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Sandra Pereira Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Anu Shah Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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I George Fantus Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Jamie W Joseph Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Adria Giacca Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, Department of Medicine, Toronto General Research Institute, Banting and Best Diabetes Centre, Institute of Medical Science, School of Pharmacy, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8

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Introduction Obesity is associated with elevated circulating free fatty acids (FFAs) and FFAs cause insulin resistance ( Lewis et al . 2002 , Xiao et al . 2008 ). FFAs induce oxidative stress ( Nakamura et al . 2009 , Yuzefovych et al . 2010

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Nigel Turner Department of Pharmacology, School of Medical Sciences, Diabetes and Obesity Division, St Vincent's Clinical School, Department of Physiology, University of New South Wales, Sydney, New South Wales, Australia
Department of Pharmacology, School of Medical Sciences, Diabetes and Obesity Division, St Vincent's Clinical School, Department of Physiology, University of New South Wales, Sydney, New South Wales, Australia

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Gregory J Cooney Department of Pharmacology, School of Medical Sciences, Diabetes and Obesity Division, St Vincent's Clinical School, Department of Physiology, University of New South Wales, Sydney, New South Wales, Australia
Department of Pharmacology, School of Medical Sciences, Diabetes and Obesity Division, St Vincent's Clinical School, Department of Physiology, University of New South Wales, Sydney, New South Wales, Australia

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Edward W Kraegen Department of Pharmacology, School of Medical Sciences, Diabetes and Obesity Division, St Vincent's Clinical School, Department of Physiology, University of New South Wales, Sydney, New South Wales, Australia
Department of Pharmacology, School of Medical Sciences, Diabetes and Obesity Division, St Vincent's Clinical School, Department of Physiology, University of New South Wales, Sydney, New South Wales, Australia

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Clinton R Bruce Department of Pharmacology, School of Medical Sciences, Diabetes and Obesity Division, St Vincent's Clinical School, Department of Physiology, University of New South Wales, Sydney, New South Wales, Australia

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(obesity) and reduced insulin action (insulin resistance) in muscle, this article will deal with FAs as an alternative energy substrate to glucose, the relevance of this substrate competition to overall energy expenditure and an assessment of the various

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Lidong Zhai Division of Molecular and Cellular Pathology, Veterans Affairs Medical Center, Department of Pathology, The University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, Alabama 35294-0019, USA

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Joseph L Messina Division of Molecular and Cellular Pathology, Veterans Affairs Medical Center, Department of Pathology, The University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, Alabama 35294-0019, USA
Division of Molecular and Cellular Pathology, Veterans Affairs Medical Center, Department of Pathology, The University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, Alabama 35294-0019, USA

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Introduction Acute insulin resistance is common following trauma, hemorrhage, sepsis, burn, and critical illness ( Ikezu et al . 1997 , Carter 1998 , Van den Berghe et al . 2001 , Cree & Wolfe 2008 ). Chronic insulin resistant states, such as

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