Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal


Author index

Page Path
HOME > Browse > Author index
Dumitru Constantin-Teodosiu  (Constantin-Teodosiu D) 1 Article
Regulation of Muscle Pyruvate Dehydrogenase Complex in Insulin Resistance: Effects of Exercise and Dichloroacetate
Dumitru Constantin-Teodosiu
Diabetes Metab J. 2013;37(5):301-314.   Published online October 17, 2013
  • 6,618 View
  • 81 Download
  • 47 Crossref
AbstractAbstract PDFPubReader   

Since the mitochondrial pyruvate dehydrogenase complex (PDC) controls the rate of carbohydrate oxidation, impairment of PDC activity mediated by high-fat intake has been advocated as a causative factor for the skeletal muscle insulin resistance, metabolic syndrome, and the onset of type 2 diabetes (T2D). There are also situations where muscle insulin resistance can occur independently from high-fat dietary intake such as sepsis, inflammation, or drug administration though they all may share the same underlying mechanism, i.e., via activation of forkhead box family of transcription factors, and to a lower extent via peroxisome proliferator-activated receptors. The main feature of T2D is a chronic elevation in blood glucose levels. Chronic systemic hyperglycaemia is toxic and can lead to cellular dysfunction that may become irreversible over time due to deterioration of the pericyte cell's ability to provide vascular stability and control to endothelial proliferation. Therefore, it may not be surprising that T2D's complications are mainly macrovascular and microvascular related, i.e., neuropathy, retinopathy, nephropathy, coronary artery, and peripheral vascular diseases. However, life style intervention such as exercise, which is the most potent physiological activator of muscle PDC, along with pharmacological intervention such as administration of dichloroacetate or L-carnitine can prove to be viable strategies for treating muscle insulin resistance in obesity and T2D as they can potentially restore whole body glucose disposal.


Citations to this article as recorded by  
  • Oxidative stress and metabolism meet epigenetic modulation in physical exercise
    José Luis García-Giménez, Irene Cánovas-Cervera, Federico V. Pallardó
    Free Radical Biology and Medicine.2024; 213: 123.     CrossRef
  • The pyruvate dehydrogenase complex: Life’s essential, vulnerable and druggable energy homeostat
    Peter W. Stacpoole, Charles E. McCall
    Mitochondrion.2023; 70: 59.     CrossRef
  • Regulating mitochondrial metabolism by targeting pyruvate dehydrogenase with dichloroacetate, a metabolic messenger
    Nick Schoenmann, Nicholas Tannenbaum, Ryan M. Hodgeman, Raghavan Pillai Raju
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2023; 1869(7): 166769.     CrossRef
  • Serum metabolomics profiling by proton nuclear magnetic resonance spectrometry of the response to single oral macronutrient challenges in women with polycystic ovary syndrome (PCOS) compared with male and female controls
    Héctor F. Escobar-Morreale, María Ángeles Martínez-García, María Insenser, Nicolau Cañellas, Xavier Correig, Manuel Luque-Ramírez
    Biology of Sex Differences.2023;[Epub]     CrossRef
  • Metabolomics and mitochondrial dysfunction in cardiometabolic disease
    Abhishek Shastry, Kimberly Dunham-Snary
    Life Sciences.2023; 333: 122137.     CrossRef
  • Loss of metabolic flexibility as a result of overexpression of pyruvate dehydrogenase kinases in muscle, liver and the immune system: Therapeutic targets in metabolic diseases
    Jae‐Han Jeon, Themis Thoudam, Eun Jung Choi, Min‐Ji Kim, Robert A Harris, In‐Kyu Lee
    Journal of Diabetes Investigation.2021; 12(1): 21.     CrossRef
  • Targeting pyruvate dehydrogenase kinase signaling in the development of effective cancer therapy
    Saleha Anwar, Anas Shamsi, Taj Mohammad, Asimul Islam, Md. Imtaiyaz Hassan
    Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2021; 1876(1): 188568.     CrossRef
  • Effect of exercise training on skeletal muscle protein expression in relation to insulin sensitivity: Per‐protocol analysis of a randomized controlled trial (GO‐ACTIWE)
    Lea Bruhn, Rasmus Kjøbsted, Jonas Salling Quist, Anne Sofie Gram, Mads Rosenkilde, Kristine Færch, Jørgen F.P. Wojtaszewski, Bente Stallknecht, Martin Bæk Blond
    Physiological Reports.2021;[Epub]     CrossRef
  • The Mechanism behind Influenza Virus Cytokine Storm
    Yinuo Gu, Xu Zuo, Siyu Zhang, Zhuoer Ouyang, Shengyu Jiang, Fang Wang, Guoqiang Wang
    Viruses.2021; 13(7): 1362.     CrossRef
  • Suppression of Pyruvate Dehydrogenase Kinase by Dichloroacetate in Cancer and Skeletal Muscle Cells Is Isoform Specific and Partially Independent of HIF-1α
    Nives Škorja Milić, Klemen Dolinar, Katarina Miš, Urška Matkovič, Maruša Bizjak, Mojca Pavlin, Matej Podbregar, Sergej Pirkmajer
    International Journal of Molecular Sciences.2021; 22(16): 8610.     CrossRef
  • The Regulatory Roles of PPARs in Skeletal Muscle Fuel Metabolism and Inflammation: Impact of PPAR Agonism on Muscle in Chronic Disease, Contraction and Sepsis
    Hannah Crossland, Dumitru Constantin-Teodosiu, Paul L. Greenhaff
    International Journal of Molecular Sciences.2021; 22(18): 9775.     CrossRef
  • PPARα, δ and FOXO1 Gene Silencing Overturns Palmitate-Induced Inhibition of Pyruvate Oxidation Differentially in C2C12 Myotubes
    Hung-Che Chien, Despina Constantin, Paul L. Greenhaff, Dumitru Constantin-Teodosiu
    Biology.2021; 10(11): 1098.     CrossRef
  • Molecular Mechanisms of Muscle Fatigue
    Dumitru Constantin-Teodosiu, Despina Constantin
    International Journal of Molecular Sciences.2021; 22(21): 11587.     CrossRef
  • Coronavirus Disease-19 (COVID-19) and Modern Lifestyle Diseases
    Pallav Sengupta, Sulagna Dutta
    Biomedical and Pharmacology Journal.2021; 14(4): 2245.     CrossRef
  • A single bout of resistance exercise improves postprandial lipid metabolism in overweight/obese men with prediabetes
    Adam J. Bittel, Daniel C. Bittel, Bettina Mittendorfer, Bruce W. Patterson, Adewole L. Okunade, Jun Yoshino, Lane C. Porter, Nada A. Abumrad, Dominic N. Reeds, W. Todd Cade
    Diabetologia.2020; 63(3): 611.     CrossRef
  • An integrative approach to the regulation of mitochondrial respiration during exercise: Focus on high-intensity exercise
    Jose A.L. Calbet, Saúl Martín-Rodríguez, Marcos Martin-Rincon, David Morales-Alamo
    Redox Biology.2020; 35: 101478.     CrossRef
  • PPARδ and FOXO1 Mediate Palmitate-Induced Inhibition of Muscle Pyruvate Dehydrogenase Complex and CHO Oxidation, Events Reversed by Electrical Pulse Stimulation
    Hung-Che Chien, Paul L. Greenhaff, Dumitru Constantin-Teodosiu
    International Journal of Molecular Sciences.2020; 21(16): 5942.     CrossRef
  • Cancer cachexia has many symptoms but only one cause: anoxia
    Tomas Koltai
    F1000Research.2020; 9: 250.     CrossRef
  • Structural basis for the inhibition of PDK2 by novel ATP- and lipoyl-binding site targeting compounds
    Jihoon Kang, Haushabhau S. Pagire, Donguk Kang, Yo Han Song, In Kyu Lee, Kang Taek Lee, Chin-Ju Park, Jin Hee Ahn, Jungwook Kim
    Biochemical and Biophysical Research Communications.2020; 527(3): 778.     CrossRef
  • Influenza and obesity: its odd relationship and the lessons for COVID-19 pandemic
    Livio Luzi, Maria Grazia Radaelli
    Acta Diabetologica.2020; 57(6): 759.     CrossRef
  • Changes in gene expression of lactate carriers (MCT1 and CD147) in cardiac muscle of diabetic male rats: the effect of dichloroacetate and endurance training
    H. Rezaeinasab, A. Habibi, M. Nikbakht, M. Rashno, S. Shakerian
    The Ukrainian Biochemical Journal.2020; 92(5): 111.     CrossRef
  • Mitochondrial Uncoupling Coordinated With PDH Activation Safely Ameliorates Hyperglycemia via Promoting Glucose Oxidation
    Haowen Jiang, Jia Jin, Yanan Duan, Zhifu Xie, Yufeng Li, Anhui Gao, Min Gu, Xinwen Zhang, Chang Peng, Chunmei Xia, Tiancheng Dong, Hui Li, Lifang Yu, Jie Tang, Fan Yang, Jingya Li, Jia Li
    Diabetes.2019; 68(12): 2197.     CrossRef
  • Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Induced by Repeated Forced Swimming in Mice
    Takuya Ohba, Shinichi Domoto, Miyu Tanaka, Shinsuke Nakamura, Masamitsu Shimazawa, Hideaki Hara
    Biological and Pharmaceutical Bulletin.2019; 42(7): 1140.     CrossRef
  • The Beta Cell in Type 2 Diabetes
    Ashley A. Christensen, Maureen Gannon
    Current Diabetes Reports.2019;[Epub]     CrossRef
  • Reduced expression of Twist 1 is protective against insulin resistance of adipocytes and involves mitochondrial dysfunction
    Sumei Lu, Hong Wang, Rui Ren, Xiaohong Shi, Yanmei Zhang, Wanshan Ma
    Scientific Reports.2018;[Epub]     CrossRef
  • PDK4 Deficiency Suppresses Hepatic Glucagon Signaling by Decreasing cAMP Levels
    Bo-Yoon Park, Jae-Han Jeon, Younghoon Go, Hye Jin Ham, Jeong-Eun Kim, Eun Kyung Yoo, Woong Hee Kwon, Nam-Ho Jeoung, Yong Hyun Jeon, Seung-Hoi Koo, Byung-Gyu Kim, Ling He, Keun-Gyu Park, Robert A. Harris, In-Kyu Lee
    Diabetes.2018; 67(10): 2054.     CrossRef
  • Differences in Muscle Metabolism Between Triathletes and Normally Active Volunteers Investigated Using Multinuclear Magnetic Resonance Spectroscopy at 7T
    Radka Klepochová, Ladislav Valkovič, Thomas Hochwartner, Christoph Triska, Norbert Bachl, Harald Tschan, Siegfried Trattnig, Michael Krebs, Martin Krššák
    Frontiers in Physiology.2018;[Epub]     CrossRef
  • Defining the contribution of skeletal muscle pyruvate dehydrogenase α1 to exercise performance and insulin action
    Kristoffer Svensson, Jessica R. Dent, Shahriar Tahvilian, Vitor F. Martins, Abha Sathe, Julien Ochala, Mulchand S. Patel, Simon Schenk
    American Journal of Physiology-Endocrinology and Metabolism.2018; 315(5): E1034.     CrossRef
  • Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism
    María Isabel Hernández-Alvarez, Angels Díaz-Ramos, María Berdasco, Jeff Cobb, Evarist Planet, Diane Cooper, Agnieszka Pazderska, Krzystof Wanic, Declan O’Hanlon, Antonio Gomez, Laura R. de la Ballina, Manel Esteller, Manuel Palacin, Donal J. O’Gorman, Joh
    Scientific Reports.2017;[Epub]     CrossRef
  • Therapeutic Targeting of the Pyruvate Dehydrogenase Complex/Pyruvate Dehydrogenase Kinase (PDC/PDK) Axis in Cancer
    Peter W Stacpoole
    JNCI: Journal of the National Cancer Institute.2017;[Epub]     CrossRef
  • Hyperpalatable Diet and Physical Exercise Modulate the Expression of the Glial Monocarboxylate Transporters MCT1 and 4
    Luis V. Portela, Andressa W. Brochier, Clarissa B. Haas, Afonso Kopczynski de Carvalho, Jussania A. Gnoato, Eduardo R. Zimmer, Eduardo Kalinine, Luc Pellerin, Alexandre P. Muller
    Molecular Neurobiology.2017; 54(8): 5807.     CrossRef
  • Mitochondrial targeting by dichloroacetate improves outcome following hemorrhagic shock
    Kumar Subramani, Sumin Lu, Marie Warren, Xiaogang Chu, Haroldo A. Toque, R. William Caldwell, Michael P. Diamond, Raghavan Raju
    Scientific Reports.2017;[Epub]     CrossRef
  • The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate‐intensity exercise in human skeletal muscle
    A. Vigelsø, M. Gram, R. Dybboe, A. B. Kuhlman, C. Prats, P. L. Greenhaff, D. Constantin‐Teodosiu, J. B. Birk, J. F. P. Wojtaszewski, F. Dela, J. W. Helge
    The Journal of Physiology.2016; 594(8): 2339.     CrossRef
  • Global Kinetic Analysis of Mammalian E3 Reveals pH-dependent NAD+/NADH Regulation, Physiological Kinetic Reversibility, and Catalytic Optimum
    Michael A. Moxley, Daniel A. Beard, Jason N. Bazil
    Journal of Biological Chemistry.2016; 291(6): 2712.     CrossRef
  • Pyruvate dehydrogenase kinase regulates hepatitis C virus replication
    Gwon-Soo Jung, Jae-Han Jeon, Yeon-Kyung Choi, Se Young Jang, Soo Young Park, Sung-Woo Kim, Jun-Kyu Byun, Mi-Kyung Kim, Sungwoo Lee, Eui-Cheol Shin, In-Kyu Lee, Yu Na Kang, Keun-Gyu Park
    Scientific Reports.2016;[Epub]     CrossRef
  • Altered heart proteome in fructose-fed Fisher 344 rats exposed to bisphenol A
    S.A. Ljunggren, M. Iggland, M. Rönn, L. Lind, P.M. Lind, H. Karlsson
    Toxicology.2016; 347-349: 6.     CrossRef
  • Unacylated ghrelin restores insulin and autophagic signaling in skeletal muscle of diabetic mice
    Bjorn T. Tam, Xiao M. Pei, Benjamin Y. Yung, Shea P. Yip, Lawrence W. Chan, Cesar S. Wong, Parco M. Siu
    Pflügers Archiv - European Journal of Physiology.2015; 467(12): 2555.     CrossRef
  • Sex-related differences in the effects of high-fat diets on DHEA-treated rats
    Ana Lúcia Cecconello, Marcia Trapp, Ana Lúcia Hoefel, Cláudia Vieira Marques, Bruno Dutra Arbo, Gabriela Osterkamp, Luiz Carlos Rios Kucharski, Maria Flávia Marques Ribeiro
    Endocrine.2015; 48(3): 985.     CrossRef
  • Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle
    Sergio Arrabal, Miguel Angel Lucena, Miren Josune Canduela, Almudena Ramos-Uriarte, Patricia Rivera, Antonia Serrano, Francisco Javier Pavón, Juan Decara, Antonio Vargas, Elena Baixeras, Mercedes Martín-Rufián, Javier Márquez, Pedro Fernández-Llébrez, Bau
    PLOS ONE.2015; 10(12): e0145244.     CrossRef
  • A glance at … exercise and glucose uptake
    Michael J. Glade, Kyl Smith
    Nutrition.2015; 31(6): 893.     CrossRef
  • Perpetual muscle PDH activation in PDH kinase knockout mice protects against high-fat feeding–induced muscle insulin resistance
    Dumitru Constantin-Teodosiu, Francis B. Stephens, Paul L. Greenhaff
    Proceedings of the National Academy of Sciences.2015;[Epub]     CrossRef
  • Statin-Induced Increases in Atrophy Gene Expression Occur Independently of Changes in PGC1α Protein and Mitochondrial Content
    Craig A. Goodman, Derk Pol, Evelyn Zacharewicz, Robert S. Lee-Young, Rod J. Snow, Aaron P. Russell, Glenn K. McConell, Ashok Kumar
    PLOS ONE.2015; 10(5): e0128398.     CrossRef
  • 13C metabolic flux analysis shows that resistin impairs the metabolic response to insulin in L6E9 myotubes
    Shirley Guzmán, Silvia Marin, Anibal Miranda, Vitaly A Selivanov, Josep J Centelles, Romain Harmancey, Fatima Smih, Annie Turkieh, Yves Durocher, Antonio Zorzano, Philippe Rouet, Marta Cascante
    BMC Systems Biology.2014;[Epub]     CrossRef
  • Translational Research: From Biological Discovery to Public Benefit (or Not)
    Michael R. Emmert-Buck
    Advances in Biology.2014; 2014: 1.     CrossRef
  • Diabetic Worker with History of Falls: A Case Study
    Ann R. Lurati
    Workplace Health & Safety.2014; 62(5): 175.     CrossRef
  • Diabetic Worker With History of Falls: A Case Study
    Ann R. Lurati
    Workplace Health & Safety.2014; 62(5): 175.     CrossRef
  • Mitochondrial Pyruvate Carrier 2 Hypomorphism in Mice Leads to Defects in Glucose-Stimulated Insulin Secretion
    Patrick A. Vigueira, Kyle S. McCommis, George G. Schweitzer, Maria S. Remedi, Kari T. Chambers, Xiaorong Fu, William G. McDonald, Serena L. Cole, Jerry R. Colca, Rolf F. Kletzien, Shawn C. Burgess, Brian N. Finck
    Cell Reports.2014; 7(6): 2042.     CrossRef

Diabetes Metab J : Diabetes & Metabolism Journal
Close layer