Glucose transport in the heart

Abstract

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.