The facilitative glucose transporter GLUT3: 20 years of distinction

1 Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; 2 Departments of Psychiatry and Pharmacology, Louisiana State University Health Sciences Center, Shreveport, Louisiana; 3 National Institutes of Heart, Lung, Blood/National Institutes of Health, Bethesda, Maryland; 4 Department of Obstetrics/Gynecology, Washington University, St. Louis, Missouri; 5 Baker Institute for Animal Health, Cornell University, Ithaca, New York; and 6 Department of Pediatrics/Newborn Medicine, Weill Cornell Medical College, New York, New York Submitted 23 April 2008 ; accepted in final form 19 June 2008 ABSTRACT Glucose metabolism is vital to most mammalian cells, and the passage of glucose across cell membranes is facilitated by a family of integral membrane transporter proteins, the GLUTs. There are currently 14 members of the SLC2 family of GLUTs, several of which have been the focus of this series of reviews. The subject of the present review is GLUT3, which, as implied by its name, was the third glucose transporter to be cloned (Kayano T, Fukumoto H, Eddy RL, Fan YS, Byers MG, Shows TB, Bell GI. J Biol Chem 263: 15245–15248, 1988) and was originally designated as the neuronal GLUT. The overriding question that drove the early work on GLUT3 was why would neurons need a separate glucose transporter isoform? What is it about GLUT3 that specifically suits the needs of the highly metabolic and oxidative neuron with its high glucose demand? More recently, GLUT3 has been studied in other cell types with quite specific requirements for glucose, including sperm, preimplantation embryos, circulating white blood cells, and an array of carcinoma cell lines. The last are sufficiently varied and numerous to warrant a review of their own and will not be discussed here. However, for each of these cases, the same questions apply. Thus, the objective of this review is to discuss the properties and tissue and cellular localization of GLUT3 as well as the features of expression, function, and regulation that distinguish it from the rest of its family and make it uniquely suited as the mediator of glucose delivery to these specific cells. neurons; sperm; preimplantation embryo; white blood cells Address for reprint requests and other correspondence: I. A. Simpson, Dept. of Neural and Behavioral Sciences, MC H109, College of Medicine, Penn State University, C3801, 500 University Dr., Hershey, PA 17033 (e-mail: ixs10{at}psu.edu )