Most mammalian cells transport glucose through a family of membrane proteins known as glucose transporters. Molecular cloning of these glucose transporters has identified a family of closely related genes that encodes at least 7 proteins (Glut-1 to Glut-7, MW. 40-60kD) and Sodium glucose co-transporter-1 (SGLT-1, 662 amino acids; ~75kD). Individual member of this family have identical predicted secondary structures with 12 transmembrane domains. Both N and c-termini are predicted to be cytoplasmic. Most differences in sequence homology exist within the four hydrophilic domains that may play a role in tissue-specific targeting. Glut isoforms differ in their tissue expression, substrate specificity and kinetic characteristics. Glut-1 mediates glucose transport into red cells, and throughout the blood brain barrier, and supply glucose to most cells. Glut-2 provides glucose to the liver and pancreatic cells. Glut-3 is the main transporter in neurons, whereas Glut-4 is primarily expressed in muscle and adipose tissue and regulated by insulin. Glut-5 transports fructose in intestine and testis. Glut-6 is a pseudoegene and unlikely to be expressed at the protein level. Glut-7, expressed in liver and other gluconeogenic tissues, mediates glucose flux across endoplasmic reticulum membrane. Glut-8 is found in adult testis and placenta. Human Glut-9 is expressed in spleen, peripheral leucocytes and brain. Human Glut-10 (541 aa, chromosome 20q13.1; ~30-35% homology with Glut-3 and Glut-8) has been identified as a candidate gene for NIDDM susceptibility. It is widely expressed with highest levels in liver and pancreas. Glut-11 (496 aa, chromosome 22q11.2; ~41% identity with Glut-5) is expressed in heart and skeletal muscle.
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