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Myocardial glycophagy flux dysregulation and glycogen accumulation characterize diabetic cardiomyopathy.
Mellor, Kimberley M; Varma, Upasna; Koutsifeli, Parisa; Daniels, Lorna J; Benson, Victoria L; Annandale, Marco; Li, Xun; Nursalim, Yohanes; Janssens, Johannes V; Weeks, Kate L; Powell, Kim L; O'Brien, Terence J; Katare, Rajesh; Ritchie, Rebecca H; Bell, James R; Gottlieb, Roberta A; Delbridge, Lea M D.
Affiliation
  • Mellor KM; Department of Physiology, University of Auckland, Auckland, New Zealand; Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand; Department of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia.
  • Varma U; Department of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia.
  • Koutsifeli P; Department of Physiology, University of Auckland, Auckland, New Zealand.
  • Daniels LJ; Department of Physiology, University of Auckland, Auckland, New Zealand; Radcliffe Department of Medicine, OCDEM, University of Oxford, United Kingdom.
  • Benson VL; Department of Physiology, University of Auckland, Auckland, New Zealand.
  • Annandale M; Department of Physiology, University of Auckland, Auckland, New Zealand.
  • Li X; Department of Physiology, University of Auckland, Auckland, New Zealand.
  • Nursalim Y; Department of Physiology, University of Auckland, Auckland, New Zealand.
  • Janssens JV; Department of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia; Department of Biomedical Sciences, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, USA.
  • Weeks KL; Department of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Victoria, Australia.
  • Powell KL; Department of Medicine, University of Melbourne & Department of Neuroscience, Central Clinical School Monash University, Melbourne, Victoria, Australia.
  • O'Brien TJ; Department of Medicine, University of Melbourne & Department of Neuroscience, Central Clinical School Monash University, Melbourne, Victoria, Australia.
  • Katare R; Department of Physiology, Heart Otago, University of Otago, Dunedin, New Zealand.
  • Ritchie RH; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Victoria, Australia; Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Victoria, Australia.
  • Bell JR; Department of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia; Department of Microbiology, Anatomy, Physiology & Pharmacology, La Trobe University, Australia.
  • Gottlieb RA; Department of Biomedical Sciences, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, USA.
  • Delbridge LMD; Department of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia. Electronic address: lmd@unimelb.edu.au.
J Mol Cell Cardiol ; 189: 83-89, 2024 Apr.
Article in En | MEDLINE | ID: mdl-38484473
ABSTRACT
Diabetic heart disease morbidity and mortality is escalating. No specific therapeutics exist and mechanistic understanding of diabetic cardiomyopathy etiology is lacking. While lipid accumulation is a recognized cardiomyocyte phenotype of diabetes, less is known about glycolytic fuel handling and storage. Based on in vitro studies, we postulated the operation of an autophagy pathway in the myocardium specific for glycogen homeostasis - glycophagy. Here we visualize occurrence of cardiac glycophagy and show that the diabetic myocardium is characterized by marked glycogen elevation and altered cardiomyocyte glycogen localization. We establish that cardiac glycophagy flux is disturbed in diabetes. Glycophagy may represent a potential therapeutic target for alleviating the myocardial impacts of metabolic disruption in diabetic heart disease.
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Full text: 1 Database: MEDLINE Main subject: Diabetes Mellitus / Diabetic Cardiomyopathies Limits: Humans Language: En Year: 2024 Type: Article
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PubMed Links
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Full text: 1 Database: MEDLINE Main subject: Diabetes Mellitus / Diabetic Cardiomyopathies Limits: Humans Language: En Year: 2024 Type: Article