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Jordan S F Chan
Jordan S F Chan
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Amanda A Greenwell
Amanda A Greenwell
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Christina T Saed
Christina T Saed
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Magnus J Stenlund
Magnus J Stenlund
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Indiresh A Mangra-Bala
Indiresh A Mangra-Bala
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Seyed Amirhossein Tabatabaei Dakhili
Seyed Amirhossein Tabatabaei Dakhili
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Kunyan Yang
Kunyan Yang
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Sally R Ferrari
Sally R Ferrari
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Farah Eaton
Farah Eaton
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Keshav Gopal
Keshav Gopal
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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John R Ussher
John R Ussher
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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oxidation secondary to the stimulation of pyruvate dehydrogenase (PDH) activity ( Almutairi et al. 2021 ), the rate-limiting enzyme of glucose oxidation ( Patel et al. 2014 ). These actions on myocardial glucose oxidation appear to be indirectly mediated
MC Sugden
MC Sugden
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HS Lall
HS Lall
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RA Harris
RA Harris
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MJ Holness
MJ Holness
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The pyruvate dehydrogenase kinases (PDK1-4) regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC). Immunoblot analysis with antibodies raised against recombinant PDK isoforms demonstrated changes in PDK isoform expression in response to experimental hyperthyroidism (100 microg/100 g body weight; 3 days) that was selective for fast-twitch vs slow-twitch skeletal muscle in that PDK2 expression was increased in the fast-twitch skeletal muscle (the anterior tibialis) (by 1. 6-fold; P<0.05) but not in the slow-twitch muscle (the soleus). PDK4 protein expression was increased by experimental hyperthyroidism in both muscle types, there being a greater response in the anterior tibialis (4.2-fold increase; P<0.05) than in the soleus (3.2-fold increase; P<0.05). The hyperthyroidism-associated up-regulation of PDK4 expression was observed in conjunction with suppression of skeletal-muscle PDC activity, but not suppression of glucose uptake/phosphorylation, as measured in vivo in conscious unrestrained rats (using the 2-[(3)H]deoxyglucose technique). We propose that increased PDK isoform expression contributes to the pathology of hyperthyroidism and to PDC inactivation by facilitating the operation of the glucose --> lactate --> glucose (Cori) and glucose --> alanine --> glucose cycles. We also propose that enhanced relative expression of the pyruvate-insensitive PDK isoform (PDK4) in skeletal muscle in hyperthyroidism uncouples glycolytic flux from pyruvate oxidation, sparing pyruvate for non-oxidative entry into the tricarboxylic acid (TCA) cycle, and thereby supporting entry of acetyl-CoA (derived from fatty acid oxidation) into the TCA cycle.
Natalia Pavón
Natalia Pavón
Departamento de Farmacología, Instituto Nacional de Cardiología Ignacio Chávez, México, Mexico
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Alfredo Cabrera-Orefice
Alfredo Cabrera-Orefice
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., Mexico
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Juan Carlos Gallardo-Pérez
Juan Carlos Gallardo-Pérez
Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, México, Mexico
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Cristina Uribe-Alvarez
Cristina Uribe-Alvarez
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., Mexico
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Nadia A Rivero-Segura
Nadia A Rivero-Segura
Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química UNAM, México D.F., Mexico
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Edgar Ricardo Vazquez-Martínez
Edgar Ricardo Vazquez-Martínez
Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química UNAM, México D.F., Mexico
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Marco Cerbón
Marco Cerbón
Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química UNAM, México D.F., Mexico
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Eduardo Martínez-Abundis
Eduardo Martínez-Abundis
División Académica Multidisciplinaria de Comalcalco, Universidad Juárez Autónoma de Tabasco, México, Mexico
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Juan Carlos Torres-Narvaez
Juan Carlos Torres-Narvaez
Departamento de Farmacología, Instituto Nacional de Cardiología Ignacio Chávez, México, Mexico
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Raúl Martínez-Memije
Raúl Martínez-Memije
Departamento de Instrumentación Electromecánica, Instituto Nacional de Cardiología Ignacio Chávez, Tlalpan DF, México, Mexico
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Francisco-Javier Roldán-Gómez
Francisco-Javier Roldán-Gómez
Departamento de Consulta externa, Instituto Nacional de Cardiología Ignacio Chávez, México, Mexico
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Salvador Uribe-Carvajal
Salvador Uribe-Carvajal
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., Mexico
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capacity and antioxidant defenses ( Nadal-Casellas et al . 2011 ), as well as complex IV (COX) and pyruvate dehydrogenase (PDH) activities in whole-brain mitochondria ( Irwin et al . 2011 ). However, these changes have not been fully explored in heart
Brenna Osborne
Brenna Osborne
Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
Department of Pharmacology, School of Biomedical Sciences, UNSW Sydney, New South Wales, Australia
Department of Cellular and Molecular Medicine, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Department of Pharmacology, School of Biomedical Sciences, UNSW Sydney, New South Wales, Australia
Department of Cellular and Molecular Medicine, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Lauren E Wright
Lauren E Wright
Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
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Amanda E Brandon
Amanda E Brandon
Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
Charles Perkins Centre, University of Sydney, New South Wales, Australia
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Charles Perkins Centre, University of Sydney, New South Wales, Australia
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Ella Stuart
Ella Stuart
Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
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Lewin Small
Lewin Small
Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
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Joris Hoeks
Joris Hoeks
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands
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Patrick Schrauwen
Patrick Schrauwen
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands
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David A Sinclair
David A Sinclair
Department of Genetics, Paul F. Glenn Center for Biology of Aging Research, Harvard Medical School, Boston, Massachusetts, USA
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Magdalene K Montgomery
Magdalene K Montgomery
Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
Department of Anatomy & Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
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Department of Anatomy & Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
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Gregory J Cooney
Gregory J Cooney
Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
Charles Perkins Centre, University of Sydney, New South Wales, Australia
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Charles Perkins Centre, University of Sydney, New South Wales, Australia
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Nigel Turner
Nigel Turner
Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
Department of Pharmacology, School of Biomedical Sciences, UNSW Sydney, New South Wales, Australia
Cellular Bioenergetics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
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Department of Pharmacology, School of Biomedical Sciences, UNSW Sydney, New South Wales, Australia
Cellular Bioenergetics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
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presence of 0 mM, 0.2 mM, 0.5 mM, 1 mM or 2 mM pyruvate. Oxidative enzyme activity The maximal activity of citrate synthase (CS), succinate dehydrogenase (SDH), hexokinase (HK), isocitrate dehydrogenase (IDH) and active pyruvate dehydrogenase (PDH
Ricardo J Samms
Ricardo J Samms
School of Life Sciences, Lilly Research Laboratories, Chemistry Department, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
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Michelle Murphy
Michelle Murphy
School of Life Sciences, Lilly Research Laboratories, Chemistry Department, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
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Maxine J Fowler
Maxine J Fowler
School of Life Sciences, Lilly Research Laboratories, Chemistry Department, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
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Scott Cooper
Scott Cooper
School of Life Sciences, Lilly Research Laboratories, Chemistry Department, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
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Paul Emmerson
Paul Emmerson
School of Life Sciences, Lilly Research Laboratories, Chemistry Department, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
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Tamer Coskun
Tamer Coskun
School of Life Sciences, Lilly Research Laboratories, Chemistry Department, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
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Andrew C Adams
Andrew C Adams
School of Life Sciences, Lilly Research Laboratories, Chemistry Department, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
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Alexei Kharitonenkov
Alexei Kharitonenkov
School of Life Sciences, Lilly Research Laboratories, Chemistry Department, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
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Francis J P Ebling
Francis J P Ebling
School of Life Sciences, Lilly Research Laboratories, Chemistry Department, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
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Kostas Tsintzas
Kostas Tsintzas
School of Life Sciences, Lilly Research Laboratories, Chemistry Department, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
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dehydrogenase complex activity (PDC, mmol/min per kg dm), (B) acetylcarnitine (mmol/kg dm) and (C) pyruvate dehydrogenase 4 (PDK4) at the end of the 14-day treatment period. Values are group means± s.e.m. * P <0.05 vs vehicle. Figure 4 The effect of vehicle ( n
Cristina Mora
Cristina Mora
Biochemistry, Faculty of Science and Technological Chemistry, and Regional Centre for Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), Ciudad Real, Spain
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Cristina Pintado
Cristina Pintado
Biochemistry, Faculty of Environmental Sciences and and CRIB, UCLM, Toledo, Spain
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Blanca Rubio
Blanca Rubio
Biochemistry, Faculty of Science and Technological Chemistry, and Regional Centre for Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), Ciudad Real, Spain
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Lorena Mazuecos
Lorena Mazuecos
Biochemistry, Faculty of Science and Technological Chemistry, and Regional Centre for Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), Ciudad Real, Spain
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Virginia López
Virginia López
Biochemistry, Faculty of Science and Technological Chemistry, and Regional Centre for Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), Ciudad Real, Spain
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Alejandro Fernández
Alejandro Fernández
Biochemistry, Faculty of Science and Technological Chemistry, and Regional Centre for Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), Ciudad Real, Spain
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Aurora Salamanca
Aurora Salamanca
Biochemistry, Faculty of Science and Technological Chemistry, and Regional Centre for Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), Ciudad Real, Spain
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Brenda Bárcena
Brenda Bárcena
Biochemistry, Faculty of Science and Technological Chemistry, and Regional Centre for Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), Ciudad Real, Spain
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Teresa Fernández-Agulló
Teresa Fernández-Agulló
Health Sciences Faculty, University Rey Juan Carlos, Alcorcón, Madrid, Spain
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Carmen Arribas
Carmen Arribas
Biochemistry, Faculty of Environmental Sciences and and CRIB, UCLM, Toledo, Spain
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Nilda Gallardo
Nilda Gallardo
Biochemistry, Faculty of Science and Technological Chemistry, and Regional Centre for Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), Ciudad Real, Spain
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Antonio Andrés
Antonio Andrés
Biochemistry, Faculty of Science and Technological Chemistry, and Regional Centre for Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), Ciudad Real, Spain
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of PDK4 expression might suggest a decrease in glucose oxidation through pyruvate dehydrogenase. Nevertheless, we studied an alternate route for glucose oxidation, the anaplerotic cytoplasmic malic enzyme, as a compensatory pathway that may contribute
Firoozeh Salehzadeh
Firoozeh Salehzadeh
Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 77 Stockholm, Sweden
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Anna Rune
Anna Rune
Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 77 Stockholm, Sweden
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Megan Osler
Megan Osler
Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 77 Stockholm, Sweden
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Lubna Al-Khalili
Lubna Al-Khalili
Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 77 Stockholm, Sweden
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transporter 4; GLUT4 ( SLC2A4 ) and pyruvate dehydrogenase kinase isozyme 4 ( PDK4 ), carnitine palmitoyltransferase 1 ( CPT1 ), IRS2 , stearoyl-CoA desaturase ( SCD ), peroxisome proliferator-activated receptor delta ( PPARD ) and gamma ( PPARG ), fatty acid
Olivier Dumortier
Olivier Dumortier
Université Côte d’Azur, Inserm, CNRS, IRCAN, Nice, France
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Gaia Fabris
Gaia Fabris
Université Côte d’Azur, Inserm, CNRS, IRCAN, Nice, France
Université Côte d’Azur, CNRS, LP2M, Nice, France
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Université Côte d’Azur, CNRS, LP2M, Nice, France
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Didier F Pisani
Didier F Pisani
Université Côte d’Azur, CNRS, LP2M, Nice, France
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Virginie Casamento
Virginie Casamento
Université Côte d’Azur, Inserm, CNRS, IRCAN, Nice, France
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Nadine Gautier
Nadine Gautier
Université Côte d’Azur, Inserm, CNRS, IRCAN, Nice, France
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Charlotte Hinault
Charlotte Hinault
Université Côte d’Azur, CHU, Inserm, CNRS, IRCAN, Nice, France
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Patricia Lebrun
Patricia Lebrun
Université Côte d’Azur, Inserm, CNRS, IRCAN, Nice, France
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Christophe Duranton
Christophe Duranton
Université Côte d’Azur, CNRS, LP2M, Nice, France
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Michel Tauc
Michel Tauc
Université Côte d’Azur, CNRS, LP2M, Nice, France
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Stéphane Dalle
Stéphane Dalle
INSERM U1191, Institute of Functional Genomics (IGF), CNRS UMR5203, Montpellier University, Montpellier, France
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Julie Kerr-Conte
Julie Kerr-Conte
Translational Research for Diabetes, University of Lille, INSERM, CHRU Lille, Lille, France
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François Pattou
François Pattou
Translational Research for Diabetes, University of Lille, INSERM, CHRU Lille, Lille, France
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Marc Prentki
Marc Prentki
CRCHUM and Montreal Diabetes Research Center, Departments of Nutrition and Biochemistry and Molecular Medicine, University of Montreal, Montreal, Canada
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Emmanuel Van Obberghen
Emmanuel Van Obberghen
Université Côte d’Azur, CNRS, LP2M, Nice, France
Université Côte d’Azur, CHU, Inserm, CNRS, IRCAN, Nice, France
Université Côte d’Azur, CHU, CNRS, LP2M, Nice, France
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Université Côte d’Azur, CHU, Inserm, CNRS, IRCAN, Nice, France
Université Côte d’Azur, CHU, CNRS, LP2M, Nice, France
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pyruvate ( Fig. 4E ). In differentiated beta cells, pyruvate is slightly reduced to lactate and hence most of the glucose-derived pyruvate is metabolized in the mitochondria via pyruvate dehydrogenase and anaplerotic reactions ( Ainscow et al . 2000
Richard R Almon
Richard R Almon
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Debra C DuBois
Debra C DuBois
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Jin Y Jin
Jin Y Jin
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William J Jusko
William J Jusko
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section of the tree containing these three probe sets (Fig. 3 , middle) shows that two of the probe sets are for uncoupling protein 3 (UCP3) and one is for pyruvate dehydrogenase kinase isoenzyme 4 (PDK4). Figure 3 (right) shows an enlargement of the
Jordan S F Chan
Jordan S F Chan
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Tanin Shafaati
Tanin Shafaati
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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John R Ussher
John R Ussher
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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glucose uptake is a key contributor to the T2D-mediated decline in myocardial glucose oxidation, there are also several important molecular factors at play. The most important is the marked impairment in the activity of pyruvate dehydrogenase (PDH), the
