Glucose uptake is the process by which glucose molecules are transported from the bloodstream into cells through specialized membrane proteins called glucose transporters, primarily via facilitated diffusion or active transport mechanisms:

Facilitated Diffusion is a passive process that relies on carrier proteins to transport glucose down a concentration gradient.

Secondary Active Transport is transport of a solute in the direction of increasing electrochemical potential via the facilitated diffusion of a second solute (usually an ion, in this case Na⁺) in the direction of decreasing electrochemical potential. This gradient is established via primary active transport of Na⁺ ions (a process which requires ATP).

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. Among them, GLUT1-5 are the most extensively studied. However, for study GLUTs 1-4 or the Class I GLUTs are the most relevant. For more information on other GLUTs see sources 3 and 7, or the GLUT specific wikipedia pages.

GLUT1 is a hydrophobic protein and 50% of GLUT1 is in the lipid bilayer. GLUT1 is present in the placenta, brain, epithelial cells of the mammary gland, transformed cells, and fetal tissue. Due to its ubiquitous presence, it is proposed that GLUT1 is at least somewhat responsible for basal glucose uptake. Basal blood glucose levels are approximately 5 mM (milimolar). The Km value—which indicates the affinity of a transporter for glucose—is 1 mM for GLUT1 and GLUT3. Since a lower Km value corresponds to a higher affinity, these transporters have a strong ability to bind and transport glucose even at low concentrations. As a result, GLUT1 facilitates a consistent glucose uptake from the bloodstream, ensuring a steady supply to tissues that rely on glucose.

GLUT2 in contrast has a high Km value (15-20mM) and therefore a low affinity for glucose. They are located in the plasma membranes of hepatocytes and pancreatic beta cells (in mice, but GLUT1 in human beta cells). 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.