Effect of blood glucose level on standardized uptake value (SUV) in 18F- FDG PET-scan: a systematic review and meta-analysis of 20,807 individual SUV measurements

The number of known glucose transporters has expanded considerably over the past 2 years. At least three, and up to six, Na+-dependent glucose transporters (SGLT1-SGLT6; gene name SLC5A) have been identified. Similarly, thirteen members of the family of facilitative sugar transporters (GLUT1-GLUT12 and HMIT; gene name SLC2A) are now recognised. These various transporters exhibit different substrate specificities, kinetic properties and tissue expression profiles. The number of distinct gene products, together with the presence of several different transporters in certain tissues and cells (for example, GLUT1, GLUT4, GLUT5, GLUT8, GLUT12 and HMIT in white adipose tissue), indicates that glucose delivery into cells is a process of considerable complexity.

The first identified biochemical hallmark of tumor cells was a shift in glucose metabolism from oxidative phosphorylation to aerobic glycolysis. We now know that much of this metabolic conversion is controlled by specific transcriptional programs. Recent studies suggest that activation of the hypoxia-inducible factor (HIF) is a common consequence of a wide variety of mutations underlying human cancer. HIF stimulates expression of glycolytic enzymes and decreases reliance on mitochondrial oxidative phosphorylation in tumor cells, which occurs even under aerobic conditions. In addition, recent efforts have also connected the master metabolic regulator AMP-activated protein kinase (AMPK) to several human tumor suppressors. Several promising therapeutic strategies based on modulation of AMPK, HIF and other metabolic targets have been proposed to exploit the addiction of tumor cells to increased glucose uptake and glycolysis.

In the human body, glycogen is a branched polymer of glucose stored mainly in the liver and the skeletal muscle that supplies glucose to the blood stream during fasting periods and to the muscle cells during muscle contraction. Glycogen has been identified in other tissues such as brain, heart, kidney, adipose tissue, and erythrocytes, but glycogen function in these tissues is mostly unknown. Glycogen synthesis requires a series of reactions that include glucose entrance into the cell through transporters, phosphorylation of glucose to glucose 6-phosphate, isomerization to glucose 1-phosphate, and formation of uridine 5ʹ-diphosphate-glucose, which is the direct glucose donor for glycogen synthesis. Glycogenin catalyzes the formation of a short glucose polymer that is extended by the action of glycogen synthase. Glycogen branching enzyme introduces branch points in the glycogen particle at even intervals. Laforin and malin are proteins involved in glycogen assembly but their specific function remains elusive in humans. Glycogen is accumulated in the liver primarily during the postprandial period and in the skeletal muscle predominantly after exercise. In the cytosol, glycogen breakdown or glycogenolysis is carried out by two enzymes, glycogen phosphorylase which releases glucose 1-phosphate from the linear chains of glycogen, and glycogen debranching enzyme which untangles the branch points. In the lysosomes, glycogen degradation is catalyzed by α-glucosidase. The glucose 6-phosphatase system catalyzes the dephosphorylation of glucose 6-phosphate to glucose, a necessary step for free glucose to leave the cell. Mutations in the genes encoding the enzymes involved in glycogen metabolism cause glycogen storage diseases.