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.
Department of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia.
J Mol Cell Cardiol. 2024 Apr;189:83-89. doi: 10.1016/j.yjmcc.2024.02.009. Epub 2024 Mar 13.
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.
糖尿病性心脏病的发病率和死亡率正在不断上升。目前尚无特效疗法，对糖尿病性心肌病发病机制的了解也很缺乏。虽然脂质积累是糖尿病患者心肌细胞的一种公认表型，但对于糖酵解燃料的处理和储存了解较少。基于体外研究，我们推测在心肌细胞中存在一种特定于糖原稳态的自噬途径——糖酵解。本文中，我们观察到心脏糖酵解的发生，并证实糖尿病心肌的特征是明显的糖原升高和心肌细胞糖原定位改变。我们确定糖尿病中糖酵解通量受到干扰。糖酵解可能是缓解糖尿病性心脏病代谢紊乱对心肌影响的一个有潜力的治疗靶点。
