Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
Molecules. 2018 Apr 1;23(4):807. doi: 10.3390/molecules23040807.
High glucose-induced cardiomyocyte death is a common symptom in advanced-stage diabetic patients, while its metabolic mechanism is still poorly understood. The aim of this study was to explore metabolic changes in high glucose-induced cardiomyocytes and the heart of streptozotocin-induced diabetic rats by ¹H-NMR-based metabolomics. We found that high glucose can promote cardiomyocyte death both in vitro and in vivo studies. Metabolomic results show that several metabolites exhibited inconsistent variations in vitro and in vivo. However, we also identified a series of common metabolic changes, including increases in branched-chain amino acids (BCAAs: leucine, isoleucine and valine) as well as decreases in aspartate and creatine under high glucose condition. Moreover, a reduced energy metabolism could also be a common metabolic characteristic, as indicated by decreases in ATP in vitro as well as AMP, fumarate and succinate in vivo. Therefore, this study reveals that a decrease in energy metabolism and an increase in BCAAs metabolism could be implicated in high glucose-induced cardiomyocyte death.
高糖诱导的心肌细胞死亡是晚期糖尿病患者的常见症状，但其代谢机制仍不清楚。本研究旨在通过基于 1H-NMR 的代谢组学方法探讨高糖诱导的心肌细胞和链脲佐菌素诱导的糖尿病大鼠心脏的代谢变化。我们发现高糖可促进体外和体内的心肌细胞死亡。代谢组学结果表明，一些代谢物在体外和体内表现出不一致的变化。然而，我们还鉴定出一系列共同的代谢变化，包括在高糖条件下支链氨基酸（BCAAs：亮氨酸、异亮氨酸和缬氨酸）增加以及天冬氨酸和肌酸减少。此外，能量代谢减少也可能是共同的代谢特征，这表现在体外的 ATP 减少以及体内的 AMP、富马酸和琥珀酸减少。因此，本研究揭示了能量代谢减少和 BCAAs 代谢增加可能与高糖诱导的心肌细胞死亡有关。
