GLUT TRANSPORTERS AND DISEASES

Glut protein family mediate glucose transport or uptake in a wide variety of cells. The term “GLUT” is derived from glucose transporter. They are facilitative hexose transporters. GLUT transporters are uniport systems (i.e they transport only one solute such as glucose and other hexoses such as fructose.)




Glut proteins encourage cellular glucose uptake in cells and tissues where they are found. These facilitative glucose transporters form special selective pathways between three major pools of glucose viz; the blood ,the extracellular fluids and the cellular cytoplasm. Most GLUT isoforms have been cloned using techniques such as polymerase chain reaction, reverse transcriptase ,and complementary DNA.




Detailed research reveals that GLUT transporters possess the following characteristics; they possess a putative 12 transmembrane domains with both the amino (NH3+) and carboxyl (COO-) ends inside the membrane, several isoforms have been identified with the designation GLUT1, GLUT2, GLUT3, GLUT4, GLUT5, and up to GLUT 12, possess identical genome SLC2A, are expressed in a tissue and cell specific manner, and they exhibit distinct kinetic and regulatory properties that reflect their roles in cells where they are expressed.




GLUT1 (SLC2A1) is a highly expressed isoform present in almost all cells, contain 492 amino acids and a reduction in blood glucose makes GLUT1 proteins readily available, and this encourages increased flux of glucose across the blood-brain barrier, GLUT2 (SLC2A2) is expressed in hepatocytes, pancreatic β-cells, and so on. GLUT 2 has 524 amino acids. GLUT3 (SLC2A3) is found in neurons and contains 496 amino acids.




GLUT4 (SLC2A4) is expressed in adipocytes and myocytes. GLUT4 has 509 amino acids and is responsible for glucose transport in insulin-sensitive tissues. GLUT 5 (SLC2A5) is a fructose transporter found in the plasma membrane of mature spermatozoa with 501 amino acids. Sperm cells utilize fructose in seminal fluid.




GLUT6 (SLC2A6) has been found in spleen, leukocytes and brain respectively with 507 amino acids.



GLUT7 (SLC2A7) is expressed in liver microsomes and contain 528 amino acids. It encourages diffusion of free glucose in gluconeogenic tissues. GLUT8 (SLC2A8) is expressed in testis, spleen, skeletal muscle and adipose tissues. GLUT8 has 477 amino acids. GLUT9 (SLC2A9) is found expressed in the liver and kidney, has between 511 and 540 amino acids.




GLUT10 (SLC2A10) is expressed in the liver and pancreas and contains 541 amino acids. GLUT11 (SLC2A11) is found in heart and skeletal muscles. It can transport fructose and contain 496 amino acids. GLUT12 (SLC2A12) is expressed in skeletal myocytes, adipocytes and small intestine. GLUT12 encodes 617 amino acids.




Studies show that there is a correlation between GLUT transporters malfunction and diseases. GLUT2 isoform has been implicated in insulin dependent diabetes mellitus. The reason is that this isoform is present in the β-cells of the pancreas where it regulates influx of glucose through insulin secretion. Derangements in glucose homeostasis as regards GLUT4 malfunction is also linked to insulin dependent diabetes mellitus. GLUT 4 is expressed in insulin-sensitive tissues such as myocytes and adipocytes. GLUT10 has been associated with non-insulin dependent diabetes mellitus.




The link between GLUT expression and cancer has been established. Studies involving the use of tec hniques such as reverse transcriptase, polymerase chain reaction, Northern blot analysis and immunochemistry and so on have been able to detect GLUT messenger RNA (mRNA) in sarcomas and carcinomas. Hence ,in cancerous tissues ,there is an abnormal or over-expression of GLUT isoforms especially GLUT1. However ,some tumour cells express specific GLUT mRNA.