Glucose transporter

GLUTs are integral membrane proteins which contain 12 membrane spanning helices with both the amino and carboxyl termini exposed on the cytoplasmic side of the plasma membrane. GLUT proteins transport glucose and related hexoses according to a model of alternate conformation,^[3]^[4]^[5] which predicts that the transporter exposes a single substrate binding site toward either the outside or the inside of the cell. Binding of glucose to one site provokes a conformational change associated with transport, and releases glucose to the other side of the membrane. The inner and outer glucose-binding sites are probably located in transmembrane segments 9, 10, 11;^[6] also, the QLS motif located in the seventh transmembrane segment could be involved in the selection and affinity of transported substrate.^[7]^[8]

Types

Each glucose transporter isoform plays a specific role in glucose metabolism determined by its pattern of tissue expression, substrate specificity, transport kinetics, and regulated expression in different physiological conditions.^[9] To date, 13 members of the GLUT/SLC2 have been identified.^[10] On the basis of sequence similarities, the GLUT family has been divided into three subclasses.

Class I

Name	Gene	Distribution	Notes \|- \| GLUT1		Is widely distributed in fetal tissues. In the adult, it is expressed at highest levels in erythrocytes and also in the endothelial cells of barrier tissues such as the blood-brain barrier. However, it is responsible for the low-level of basal glucose uptake required to sustain respiration in all cells.	Levels in cell membranes are increased by reduced glucose levels and decreased by increased glucose levels. \|- \| GLUT2		Is expressed by renal tubular cells and small intestinal epithelial cells that transport glucose, liver cells and pancreatic ? cells. All three monosaccharides are transported from the intestinal mucosal cell into the portal circulation by GLUT2	Is a high capacity and low affinity isoform \|- \| GLUT3		Expressed mostly in neurons (where it is believed to be the main glucose transporter isoform), and in the placenta.	Is a high-affinity isoform \|- \| GLUT4		Found in adipose tissues and striated muscle (skeletal muscle and cardiac muscle).	Is the insulin-regulated glucose transporter. Responsible for insulin-regulated glucose storage.

Classes II/III

Class III comprises GLUT6 (), 8 (), 10 (), and 12 () and the H+/myoinositol transporter HMIT ().^[12]

Most members of classes II and III have been idenitified recently in homology searches of EST databases and the sequence information provided by the various genome projects.

The function of these new glucose transporter isoforms is still not clearly defined at present. Several of them (GLUT6, GLUT8) comprise motifs that help retain them intracellularly and therefore prevent glucose transport. Whether mechanisms exist to promote cell-surface translocation of these transporters is not yet known, but it has clearly been established that insulin does not promote GLUT6 and GLUT8 cell-surface translocation.