Glucose is transported across the cell membranes of adipocytes (fat cells), and its rate of transport can be speeded up 20- to 30-fold within 2 or 3 minutes by addition of insulin, without evidence of protein synthesis. Studies showed that this stimulation of glucose transport was due in part to translocation of GLUT 1 from an intracellular pool into the membrane. Careful quantitative measurements showed, however, that this could account for only a 12- to 15-fold increase in glucose transport. It became obvious that another transporter would have to be involved to account for the much larger insulin-stimulated transport. This new transporter, GLUT 4, was first identified in rat adipocytes by use of a monoclonal antibody. Subsequently, it has been cloned from rat, mouse, and human DNA (19). It is a protein with 509 amino acid residues (Tab_Le_3_._4), with 65% identity with GLUT 1, 54% identity with GLUT 2, and 58% identity with GLUT 3. Rat and mouse GLUT 4s have 95 and 96% identity, respectively, with human GLUT 4. As with the previous GLUT transporters, the two-dimensional orientation of the structure in the cell membrane is similar to that proposed for GLUT 1 (Fig 3..„3.).
GLUT 4 is the major glucose transporter of the insulin-sensitive tissues, brown and white fat, and skeletal and cardiac muscle. It occurs primarily in intracellular vesicles in the cells of these tissues. Insulin stimulation causes a rapid increase in the number of glucose transporters on the membranes of these cells because the vesicles are translocated toward the membrane and then fuse with it, releasing the molecule. This process ensures a high density of glucose transporters, enhancing the ability to move glucose from the surrounding cellular fluid into the interior of the cell, i.e., increased V max for glucose uptake. Because of this mechanism, the position of GLUT 4 and its regulation are important components of glucose homeostasis and its role in diabetes has been much studied.
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Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...