|Topic:||Glucose Transporters .|
|Details:|| One major response of non-hepatic tissues to insulin is the recruitment, to the cell surface, of glucose transporter complexes. Glucose transporters comprise a family of at least 14 members. The most well characterized members of the family are GLUT1, GLUT2, GLUT3, GLUT4 and GLUT5. The glucose transporters are facilitative transporters that carry hexose sugars across the membrane without requiring energy. These transporters belong to a family of proteins called the solute carriers. Specifically, the official gene names for the GLUTs are solute carrier family 2 (facilitated glucose transporter) member. Thus, the GLUT1 gene symbol is SLC2A1, GLUT2 is SLC2A2, GLUT3 is SLC2A3, GLUT4 is SLC2A4 and GLUT5 is SLC2A5.
There are two additional glucose transporters which are the Na+-dependent glucose transporters, SGLT1 and SGLT2 (see section above). The SGLT acronym refers to sodium-glucose linked transporter. Both SGLT1 and SGLT2 are members of the solute carrier 5 family, thus the gene encoding SGLT1 is SLC5A1 and that encoding SGLT2 is SLC5A2. These transporters are expressed in the enterocytes of the small intestine and within epithelial cells of the proximal tubules of the kidney. Within the small intestine SGLT1 contributes to dietary glucose and galactose absorption as described earlier. Within the kidney, SGLT1 is expressed in the S3 segment of the tubule and SGLT2 is expressed in the S1 and S2 segments. The activity of renal SGLT2 accounts for over 90% of the glucose reabsorption by the kidney. Due to this activity, this transporter has become a pharmacologic target for the treatment of the hyperglycemia associated with type 2 diabetes.
The GLUT family of glucose transporters can be divided into three classes based upon primary amino acid sequence comparisons. Class I transporters include GLUT1, GLUT2, GLUT3 (and the gene duplication of GLUT3 identified as GLUT14), and GLUT4. Class II transporters include GLUT5, GLUT7, GLUT9 and GLUT11. Class III transporters include GLUT6, GLUT8, GLUT10, GLUT12 and HMIT [proton (H+) myoinositol symporter: SLC2A13]. HMIT is also known as GLUT13.
GLUT1 is ubiquitously distributed in various tissues with highest levels of expression seen in brain, placenta, and erythrocytes. In fact in erythrocytes GLUT1 accounts for almost 5% of total protein. Although widely expressed, GLUT1 is not expressed in hepatocytes. GLUT1 is the primary transporter responsible for glucose transport across the blood-brain-barrier. Deficiencies in GLUT1 results in GLUT1 deficiency syndrome.
GLUT2 is found primarily in intestine, pancreatic β-cells, kidney and liver. The Km of GLUT2 for glucose (17mM) is the highest of all the sugar transporters. The high Km ensures a fast equilibrium of glucose between the cytosol and the extracellular space ensuring that liver and pancreas do not metabolize glucose until its levels rise sufficiently in the blood. GLUT2 molecules can transport both glucose and fructose. When the concentration of blood glucose increases in response to food intake, pancreatic GLUT2 molecules mediate an increase in glucose uptake which leads to increased insulin secretion. For this reason, GLUT2 is thought to be a "glucose sensor".
GLUT3 is found primarily in neurons but also found in the intestine. GLUT3 binds glucose with high affinity (has the lowest Km of the GLUTs) which allows neurons to have enhanced access to glucose especially under conditions of low blood glucose.
Insulin-sensitive tissues, such as skeletal muscle and adipose tissue, contain GLUT4 whose mobilization to the cell-surface is stimulated by insulin action.
GLUT5 and the closely related transporter GLUT7 are involved in fructose transport. GLUT5 is expressed in intestine, kidney, testes, skeletal muscle, adipose tissue and brain. Although GLUT2, -5, -7, 8, -9, -11, and -12 can all transport fructose, GLUT5 is the only transporter that exclusively transports fructose.
GLUT9 (SLC2A9) does not transport sugar but is a uric acid transporter abundant in the kidney and liver.
Recent evidence has shown that one of the cell surface binding sites for the human T cell leukemia virus (HTLV) is the ubiquitous GLUT1.
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