Wen Yi, Ma Xiaozhu, Mei Shuai, Wuyun Qidamugai, Yan Jiangtao
Department of Cardiology, Division of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China.
Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China.
Biomolecules. 2025 Jun 22;15(7):916. doi: 10.3390/biom15070916.
Diabetes mellitus (DM) is a complex global pandemic that frequently leads to multiple complications. Diabetic cardiomyopathy (DCM) is the primary cause of heart failure in patients with type 1 and 2 diabetes and is fundamentally characterized by abnormalities in myocardial structure and function. Metabolic disorders occupy a leading role in the pathogenesis of DCM, manifesting as disrupted substrate metabolism, dysregulated signaling pathways, and energy imbalance. Given the limited benefits of conventional therapeutic strategies targeting glucolipid metabolism, increasing research efforts have focused on amino acid metabolism. Amino acids are involved in the synthesis of nitrogen-containing compounds and serve as an energy source under specific conditions. Moreover, emerging studies demonstrate that metabolic disturbances of specific amino acids-such as branched-chain amino acids (BCAAs), glutamine, and arginine-exacerbate mitochondrial dysfunction and oxidative stress, thereby promoting myocardial fibrosis and cardiomyocyte injury. Therefore, this review aims to summarize the general characteristics and regulatory pathways of amino acid metabolism, as well as the specific mechanisms by which metabolic alterations of amino acids contribute to the pathogenesis and progression of diabetic cardiomyopathy, with the hope of advancing more effective translational therapeutic approaches.
糖尿病(DM)是一种复杂的全球性大流行病,常常导致多种并发症。糖尿病性心肌病(DCM)是1型和2型糖尿病患者心力衰竭的主要原因,其基本特征是心肌结构和功能异常。代谢紊乱在DCM的发病机制中起主导作用,表现为底物代谢紊乱、信号通路失调和能量失衡。鉴于针对糖脂代谢的传统治疗策略效果有限,越来越多的研究致力于氨基酸代谢。氨基酸参与含氮化合物的合成,并在特定条件下作为能量来源。此外,新出现的研究表明,特定氨基酸(如支链氨基酸(BCAAs)、谷氨酰胺和精氨酸)的代谢紊乱会加剧线粒体功能障碍和氧化应激,从而促进心肌纤维化和心肌细胞损伤。因此,本综述旨在总结氨基酸代谢的一般特征和调控途径,以及氨基酸代谢改变导致糖尿病性心肌病发病机制和进展的具体机制,以期推动更有效的转化治疗方法。