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.

Insulin and Contraction Stimulate Exocytosis, but Increased AMP-activated Protein Kinase Activity Resulting from Oxidative Metabolism Stress Slows Endocytosis of GLUT4 in Cardiomyocytes

“…In this muscle type, contraction responses on glucose transport are inhibited by wortmannin (40,44). Therefore, cardiomyocytes (although very dependent on oxidative metabolism) (30), may more closely resemble fast twitch than slow twitch skeletal muscle in the signaling responses that follow a contraction stimulus.…”

“…Stimulation of Glucose Transport in Cardiomyocytes-Heart cells are continually active, and although they can utilize a wide range of metabolic fuels, glucose supply to active heart is critical (30). Although hearts are continually contracting, increased body activity and exercise will increase the rate of heart contraction, and consequently, there will be increased demands for glucose.…”

Mammalian glucose permease GLUT1 facilitates transport of arsenic trioxide and methylarsonous acid

“…It is the major pathway for glucose uptake in many cell types, including neonatal heart, erythrocytes and the endothelial cells that form the blood-brain barrier. Although adult heart does not depend on glucose for energy, in neonatal heart, glucose utilization via GLUT1 is a major source of energy [41]. Rat GLUT1 can be functionally expressed in yeast [24], which allowed analysis of its arsenic transport properties.…”

Donepezil, Therapeutic Acetylcholinesterase Inhibitor, Prevents the Progression of Ventricular Dysfunction by Promoting Myocardial Glucose Utilization in Rat Model of Chronic Heart Failure Following Myocardial Infarction

“…When cells incorporate glucose, the transport of glucose across the plasma membrane occurs by facilitated diffusion through selective transport proteins of the GLUT family. In cardiomyocytes, the predominant glucose transport isoforms are GLUT1 and GLUT4 [35]. The GLUT1/GLUT4 ratio in rat hearts varies from 0.1 to 0.6 [36].…”