Dhalla Naranjan S, Shah Anureet K, Tappia Paramjit S
Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada.
Department of Physiology and Pathophysiology, College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.
Int J Mol Sci. 2020 Mar 31;21(7):2413. doi: 10.3390/ijms21072413.
Although the presence of cardiac dysfunction and cardiomyopathy in chronic diabetes has been recognized, the pathophysiology of diabetes-induced metabolic and subcellular changes as well as the therapeutic approaches for the prevention of diabetic cardiomyopathy are not fully understood. Cardiac dysfunction in chronic diabetes has been shown to be associated with Ca-handling abnormalities, increase in the availability of intracellular free Ca and impaired sensitivity of myofibrils to Ca. Metabolic derangements, including depressed high-energy phosphate stores due to insulin deficiency or insulin resistance, as well as hormone imbalance and ultrastructural alterations, are also known to occur in the diabetic heart. It is pointed out that the activation of the sympathetic nervous system and renin-angiotensin system generates oxidative stress, which produces defects in subcellular organelles including sarcolemma, sarcoplasmic reticulum and myofibrils. Such subcellular remodeling plays a critical role in the pathogenesis of diabetic cardiomyopathy. In fact, blockade of the effects of neurohormonal systems has been observed to attenuate oxidative stress and occurrence of subcellular remodeling as well as metabolic abnormalities in the diabetic heart. This review is intended to describe some of the subcellular and metabolic changes that result in cardiac dysfunction in chronic diabetes. In addition, the therapeutic values of some pharmacological, metabolic and antioxidant interventions will be discussed. It is proposed that a combination therapy employing some metabolic agents or antioxidants with insulin may constitute an efficacious approach for the prevention of diabetic cardiomyopathy.
尽管慢性糖尿病中心脏功能障碍和心肌病的存在已得到认可，但糖尿病诱导的代谢和亚细胞变化的病理生理学以及预防糖尿病性心肌病的治疗方法尚未完全明确。慢性糖尿病中的心脏功能障碍已被证明与钙处理异常、细胞内游离钙可用性增加以及肌原纤维对钙的敏感性受损有关。代谢紊乱，包括由于胰岛素缺乏或胰岛素抵抗导致的高能磷酸储存减少，以及激素失衡和超微结构改变，在糖尿病心脏中也会出现。有人指出，交感神经系统和肾素 - 血管紧张素系统的激活会产生氧化应激，从而导致包括肌膜、肌浆网和肌原纤维在内的亚细胞器出现缺陷。这种亚细胞重塑在糖尿病性心肌病的发病机制中起关键作用。事实上，已观察到阻断神经激素系统的作用可减轻糖尿病心脏中的氧化应激、亚细胞重塑的发生以及代谢异常。本综述旨在描述一些导致慢性糖尿病心脏功能障碍的亚细胞和代谢变化。此外，还将讨论一些药理、代谢和抗氧化干预措施的治疗价值。有人提出，将一些代谢药物或抗氧化剂与胰岛素联合使用可能构成预防糖尿病性心肌病的有效方法。
