Myocardial glycophagy flux dysregulation and glycogen accumulation characterize diabetic cardiomyopathy.

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.

• Authors: Kimberley M Mellor, Upasna Varma, Parisa Koutsifeli, Lorna J Daniels, Victoria L Benson, Marco Annandale, Xun Li, Yohanes Nursalim, Johannes V Janssens, Kate L Weeks, Kim L Powell, Terence J O'Brien, Rajesh Katare, Rebecca H Ritchie, James R Bell, Roberta A Gottlieb, Lea M D Delbridge
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 189 Pg. 83-89 (Apr 2024) ISSN: 1095-8584 [Electronic] England
• PMID: 38484473 (Publication Type: Journal Article)
• Copyright: Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Glycogen

Topics

• Humans
• Diabetic Cardiomyopathies (drug therapy)
• Myocardium (metabolism)
• Myocytes, Cardiac (metabolism)
• Glycogen (metabolism)
• Autophagy
• Diabetes Mellitus (metabolism)