Glucose for the Heart

Abstract

The homeostasis of plasma glucose levels is essential for survival of the mammalian organism. Since blood glucose concentration is maintained within a narrow range, glucose is a most reliable substrate for energy production in the heart. The importance of glucose metabolism via glycolysis is well appreciated in ischemic and hypertrophied heart muscle,1 2 3 4 but aerobic glucose metabolism for support of normal contractile function has received less attention, mainly because of the well-known fact that fatty acids are normally the predominant fuel for cardiac energy production.2 5 6 We have drawn attention to the heart as a true “omnivore,” ie, an organ that functions best when it oxidizes different substrates simultaneously.7 In light of this concept, we wish to reexamine myocardial glucose metabolism and its relevance to the human heart. In recent years, the tools of molecular and cellular biology have provided new insight into the mechanisms of glucose transport and phosphorylation. Glycogen metabolism has come into greater focus. The regulation of glycolysis is more accurately defined, and the effects of second messengers on myocardial glucose utilization are better known. In view of this background, 2 well-known clinical concepts of myocardial glucose metabolism require critical reevaluation: (1) the diagnostic concept of metabolic imaging with PET and the glucose tracer analogue 18F-2-deoxy-2-fluoro-d-glucose (FDG) and (2) the therapeutic concept of metabolic support for the postischemic heart with glucose, insulin, and K+ (GIK). The simple sugar d-glucose is the most abundant organic molecule in nature. Glucose for the heart is derived either from the bloodstream or from intracellular stores of glycogen (Figure 1⇓). The transport of glucose into the cardiomyocyte occurs along a steep concentration gradient and is regulated by specific transporters. Intracellular glucose is rapidly phosphorylated and becomes a substrate for the …