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心血管系统中的葡萄糖转运体:在健康和疾病中的作用。

Glucose transporters in cardiovascular system in health and disease.

机构信息

Institut de Recherche Expérimentale et Clinique, Pole of Cardiovascular Research, Université catholique de Louvain, Avenue Hippocrate 55, B1.55.05, B-1200, Brussels, Belgium.

Division of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

出版信息

Pflugers Arch. 2020 Sep;472(9):1385-1399. doi: 10.1007/s00424-020-02444-8. Epub 2020 Aug 18.

DOI:10.1007/s00424-020-02444-8
PMID:32809061
Abstract

Glucose transporters are essential for the heart to sustain its function. Due to its nature as a high energy-consuming organ, the heart needs to catabolize a huge quantity of metabolic substrates. For optimized energy production, the healthy heart constantly switches between various metabolites in accordance with substrate availability and hormonal status. This metabolic flexibility is essential for the maintenance of cardiac function. Glucose is part of the main substrates catabolized by the heart and its use is fine-tuned via complex molecular mechanisms that include the regulation of the glucose transporters GLUTs, mainly GLUT4 and GLUT1. Besides GLUTs, glucose can also be transported by cotransporters of the sodium-glucose cotransporter (SGLT) (SLC5 gene) family, in which SGLT1 and SMIT1 were shown to be expressed in the heart. This SGLT-mediated uptake does not seem to be directly linked to energy production but is rather associated with intracellular signalling triggering important processes such as the production of reactive oxygen species. Glucose transport is markedly affected in cardiac diseases such as cardiac hypertrophy, diabetic cardiomyopathy and heart failure. These alterations are not only fingerprints of these diseases but are involved in their onset and progression. The present review will depict the importance of glucose transport in healthy and diseased heart, as well as proposed therapies targeting glucose transporters.

摘要

葡萄糖转运体对于心脏维持其功能至关重要。由于心脏是高耗能器官,它需要分解大量代谢底物。为了实现优化的能量产生,健康的心脏会根据底物可用性和激素状态,不断在各种代谢物之间切换。这种代谢灵活性对于维持心脏功能至关重要。葡萄糖是心脏分解的主要底物之一,其利用通过包括葡萄糖转运体 GLUTs(主要是 GLUT4 和 GLUT1)调节在内的复杂分子机制进行精细调控。除了 GLUTs,葡萄糖还可以通过钠-葡萄糖协同转运蛋白(SGLT)(SLC5 基因)家族的协同转运蛋白进行转运,其中 SGLT1 和 SMIT1 已被证明在心脏中表达。这种 SGLT 介导的摄取似乎与能量产生没有直接关系,而是与触发重要过程的细胞内信号有关,如活性氧的产生。葡萄糖转运在心脏疾病(如心脏肥大、糖尿病心肌病和心力衰竭)中明显受到影响。这些改变不仅是这些疾病的特征,而且参与了它们的发生和进展。本综述将描述葡萄糖转运在健康和患病心脏中的重要性,以及针对葡萄糖转运体的治疗方法。

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