Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA.
Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE, USA.
Adv Exp Med Biol. 2018;1056:47-59. doi: 10.1007/978-3-319-74470-4_4.
Prevalence of diabetes mellitus (DM), a multifactorial disease often diagnosed with high blood glucose levels, is rapidly increasing in the world. Association of DM with multi-organ dysfunction including cardiomyopathy makes it a leading cause of morbidity and mortality. There are two major types of DM: type 1 DM (T1D) and type 2 DM (T2D). T1D is diagnosed by reduced levels of insulin and high levels of glucose in the blood. It is caused due to pancreatic beta cell destruction/loss, and mostly found in juveniles (juvenile DM). T2D is diagnosed by increased levels of insulin and glucose in the blood. It is caused due to insulin receptor dysfunction, and mostly found in the adults (adult DM). Both T1D and T2D impair cardiac muscle function, which is referred to as diabetic cardiomyopathy. We and others have reported that miRNAs, a novel class of tiny non-coding regulatory RNAs, are differentially expressed in the diabetic heart and they contribute to diabetic cardiomyopathy. Here, we elaborated the biogenesis of miRNA, how miRNA regulates a gene, cardioprotective roles of different miRNAs including miRNAs present in exosomes, underlying molecular mechanisms by which miRNA ameliorates diabetic cardiomyopathy, and the role of miRNA as a potential therapeutic target for juvenile and adult diabetic cardiomyopathy.
糖尿病(DM)是一种多因素疾病,常通过高血糖水平来诊断,其在全球的患病率正在迅速上升。DM 与包括心肌病在内的多器官功能障碍相关,使其成为发病率和死亡率的主要原因。DM 有两种主要类型:1 型糖尿病(T1D)和 2 型糖尿病(T2D)。T1D 的诊断依据是胰岛素水平降低和血液中葡萄糖水平升高。它是由于胰腺β细胞破坏/丧失引起的,主要发生在青少年(青少年 DM)中。T2D 的诊断依据是血液中胰岛素和葡萄糖水平升高。它是由于胰岛素受体功能障碍引起的,主要发生在成年人(成人 DM)中。T1D 和 T2D 都会损害心肌功能,这被称为糖尿病性心肌病。我们和其他人已经报道,miRNA 是一类新型的微小非编码调节 RNA,在糖尿病心脏中表达不同,它们有助于糖尿病性心肌病的发生。在这里,我们详细阐述了 miRNA 的生物发生、miRNA 如何调节基因、不同 miRNA 的心脏保护作用,包括外泌体中的 miRNA、miRNA 改善糖尿病性心肌病的潜在分子机制,以及 miRNA 作为青少年和成年糖尿病性心肌病潜在治疗靶点的作用。