Animal Physiology and Biochemistry Laboratory, ICMR-National Animal Resource Facility for Biomedical Research (NARFBR), Hyderabad, Telangana, 500007, India.
Center for Biological Sciences, Department of Biochemistry, K.S. Rangasamy College of Arts and Science (Autonomous), Tiruchengode, Tamil Nadu, 637215, India.
Heart Fail Rev. 2019 Mar;24(2):279-299. doi: 10.1007/s10741-018-9749-1.
Diabetic complications are among the largely exigent health problems currently. Cardiovascular complications, including diabetic cardiomyopathy (DCM), account for more than 80% of diabetic deaths. Investigators are exploring new therapeutic targets to slow or abate diabetes because of the growing occurrence and augmented risk of deaths due to its complications. Research on rodent models of type 1 and type 2 diabetes mellitus, and the use of genetic engineering techniques in mice and rats have significantly sophisticated for our understanding of the molecular mechanisms in human DCM. DCM is featured by pathophysiological mechanisms that are hyperglycemia, insulin resistance, oxidative stress, left ventricular hypertrophy, damaged left ventricular systolic and diastolic functions, myocardial fibrosis, endothelial dysfunction, myocyte cell death, autophagy, and endoplasmic reticulum stress. A number of molecular and cellular pathways, such as cardiac ubiquitin proteasome system, FoxO transcription factors, hexosamine biosynthetic pathway, polyol pathway, protein kinase C signaling, NF-κB signaling, peroxisome proliferator-activated receptor signaling, Nrf2 pathway, mitogen-activated protein kinase pathway, and micro RNAs, play a major role in DCM. Currently, there are a few drugs for the management of DCM and some of them have considerable adverse effects. So, researchers are focusing on the natural products to ameliorate it. Hence, in this review, we discuss the pathogical, molecular, and cellular mechanisms of DCM; the current diagnostic methods and treatments; adverse effects of conventional treatment; and beneficial effects of natural product-based therapeutics, which may pave the way to new treatment strategies. Graphical Abstract.
糖尿病并发症是当前亟待解决的健康问题之一。心血管并发症，包括糖尿病心肌病（DCM），占糖尿病死亡人数的 80%以上。由于其并发症的发生率不断增加和死亡风险增加，研究人员正在探索新的治疗靶点来减缓或阻止糖尿病的发展。
对 1 型和 2 型糖尿病啮齿动物模型的研究，以及在小鼠和大鼠中使用基因工程技术，极大地加深了我们对人类 DCM 分子机制的理解。DCM 的特征是病理生理机制，包括高血糖、胰岛素抵抗、氧化应激、左心室肥厚、受损的左心室收缩和舒张功能、心肌纤维化、内皮功能障碍、心肌细胞死亡、自噬和内质网应激。
许多分子和细胞途径，如心脏泛素蛋白酶体系统、FoxO 转录因子、己糖胺生物合成途径、多元醇途径、蛋白激酶 C 信号通路、NF-κB 信号通路、过氧化物酶体增殖物激活受体信号通路、Nrf2 通路、丝裂原激活蛋白激酶通路和 microRNAs，在 DCM 中起主要作用。目前，有几种药物可用于 DCM 的治疗，但其中一些药物有相当大的副作用。因此，研究人员专注于天然产物来改善它。因此，在这篇综述中，我们讨论了 DCM 的病理、分子和细胞机制；目前的诊断方法和治疗方法；传统治疗的不良反应；以及基于天然产物的治疗方法的有益效果，这可能为新的治疗策略铺平道路。
图摘要。
