Glucose uptake

Glucose transporters (GLUTs) are classified into three groups based on sequence similarity, with a total of 14 members. All GLUT proteins share a common structure: 12 transmembrane segments, a single N-linked glycosylation site, a large central cytoplasmic linker, and both N- and C-termini located in the cytoplasm. These transporters are expressed in nearly all body cells. While most GLUTs facilitate glucose transport, HMIT is an exception. Due to its ubiquitous presence, it is proposed that GLUT1 is at least somewhat responsible for basal glucose uptake. The high Km of GLUT2 allows for glucose sensing; rate of glucose entry is proportional to blood glucose levels. GLUT3 is primarily expressed in neurons, specifically in cell processes (axons and dendrites), however, it is also found in many other cells throughout the body. GLUT4 is an insulin-responsive glucose transporter located in the heart, skeletal muscle, brain, and adipose tissue. GLUT4 is generally in vesicles in the cytoplasm. In response to insulin, more GLUT4 transporters are relocated from these vesicles to the cell membrane. At the binding of insulin (released from the islets of Langerhans) to receptors on the cell surface, a signalling cascade begins by activating phosphatidylinositolkinase activity which culminates in the movement of the cytoplasmic vesicles toward the cell surface membrane. Upon reaching the plasmalemma, the vesicles fuse with the membrane, increasing the number of GLUT4 transporters expressed at the cell surface, and hence increasing glucose uptake. GLUT4 has a Km value for glucose of about 5 mM, which as stated above is the normal blood glucose level in healthy individuals. GLUT4 is the most abundant glucose transporter in skeletal muscle and is thus considered to be rate limiting for glucose uptake and metabolism in resting muscles. The drug metformin phosphorylates GLUT4, thereby increasing its sensitivity to insulin. == Secondary active transport ==

Facilitated diffusion can occur between the bloodstream and cells as the concentration gradient between the extracellular and intracellular environments is such that no ATP hydrolysis is required. However, in the kidney, glucose is reabsorbed from the filtrate in the tubule lumen, where it is at a relatively low concentration, passes through the simple cuboidal epithelia lining the kidney tubule, and into the bloodstream where glucose is at a comparatively high concentration. Therefore, the concentration gradient of glucose opposes its reabsorption, and energy is required for its transport. The secondary active transport of glucose in the kidney is Na+ linked; therefore an Na+ gradient must be established. This is achieved through the action of the Na+/K+ pump, the energy for which is provided through the hydrolysis of ATP. Once inside the epithelial cells, glucose reenters the bloodstream through facilitated diffusion through GLUT2 transporters. Hence reabsorption of glucose is dependent upon the existing sodium gradient which is generated through the active functioning of the Na+/K+-ATPase. As the cotransport of glucose with sodium from the lumen does not directly require ATP hydrolysis but depends upon the action of the ATPase, this is described as secondary active transport. SGLT1 transporters are found close to the loop of Henle and in the distal convoluted tubule of the nephron where much glucose has been reabsorbed into the bloodstream. These have a high affinity for glucose and a low capacity. Functioning in conjunction, these two secondary active transporters ensure that only negligible amounts of glucose are wasted through excretion in the urine. == References ==