Abel E Dale
Division of Endocrinology, Metabolism and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah, USA.
Front Biosci. 2004 Jan 1;9:201-15. doi: 10.2741/1216.
The heart is a unique organ in many ways. It consists of specialized muscle cells (cardiomyocytes), which are adapted to contract constantly in a coordinated fashion. This is vital to the survival of the organism given the central role of the heart in the maintenance of the cardiovascular system that delivers oxygen, metabolic substrates and hormones to the rest of the body. In order for the heart to maintain its function it must receive a constant supply of metabolic substrates, to generate ATP to maintain contractile function, without fatigue. Thus the heart is capable of utilizing a variety of metabolic substrates and is able to rapidly adapt its substrate utilization in the face of changes in substrate supply. The major metabolic substrate for the heart is fatty acids. However, up to 30% of myocardial ATP is generated by glucose and lactate, with smaller contributions from ketones and amino acids. Although glucose is not the major metabolic substrate in the heart at rest, there are many circumstances in which it assumes greater importance such as during ischemia, increased workload and pressure overload hypertrophy. Like all other cells, glucose is transported into cardiac myocytes by members of the family of facilitative glucose transporters (GLUTs). In this regard, cardiomyocytes bear many similarities to skeletal muscle, but there are also important differences. For example, the most abundant glucose transporter in the heart is the GLUT4 transporter, in which translocation to the plasma membrane represents an important mechanism by which the net flux of glucose into the cell is regulated. Because cardiomyocytes are constantly contracting it is likely that contraction mediated GLUT4 translocation represents an important mechanism that governs the entry of glucose into the heart. While this is also true in skeletal muscle, because many muscles are often at rest, insulin mediated GLUT4 translocation represents a quantitatively more important mechanism regulating skeletal muscle glucose uptake than is the case in the heart. In contrast to skeletal muscle, where most GLUT1 is in perineural sheaths (1), in the heart there is significant expression of GLUT1 (2), which under certain circumstances is responsible for a significant component of basal cardiac glucose uptake. This review will summarize the current state of knowledge regarding the regulation of glucose transporter expression, and the regulation of glucose transport into myocardial cells.
心脏在许多方面都是一个独特的器官。它由特殊的肌肉细胞（心肌细胞）组成，这些细胞能够以协调的方式持续收缩。鉴于心脏在维持心血管系统中的核心作用，而心血管系统为身体其他部位输送氧气、代谢底物和激素，所以心脏的这种持续协调收缩对生物体的生存至关重要。为了维持其功能，心脏必须持续获得代谢底物，以产生三磷酸腺苷（ATP）来维持收缩功能，且不会疲劳。因此，心脏能够利用多种代谢底物，并能在底物供应发生变化时迅速调整其底物利用情况。心脏的主要代谢底物是脂肪酸。然而，高达30%的心肌ATP由葡萄糖和乳酸产生，酮类和氨基酸的贡献较小。尽管葡萄糖在静息状态下不是心脏的主要代谢底物，但在许多情况下它会变得更加重要，比如在缺血、工作量增加和压力超负荷肥大期间。与所有其他细胞一样，葡萄糖通过易化葡萄糖转运蛋白家族（GLUTs）的成员转运到心肌细胞中。在这方面，心肌细胞与骨骼肌有许多相似之处，但也存在重要差异。例如，心脏中最丰富的葡萄糖转运蛋白是GLUT4转运蛋白，其向质膜的转位是调节葡萄糖净流入细胞的重要机制。由于心肌细胞不断收缩，收缩介导的GLUT4转位可能是控制葡萄糖进入心脏的重要机制。虽然在骨骼肌中也是如此，但由于许多肌肉经常处于静止状态，胰岛素介导的GLUT4转位在调节骨骼肌葡萄糖摄取方面比在心脏中代表着更重要的定量机制。与骨骼肌不同，在骨骼肌中大多数GLUT1存在于神经周围鞘中（1），而在心脏中GLUT1有显著表达（2），在某些情况下，它是基础心脏葡萄糖摄取的重要组成部分。本综述将总结关于葡萄糖转运蛋白表达调控以及葡萄糖转运入心肌细胞调控的当前知识状态。
