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The 'Other class I/III GLUTs' refers to a broad group of proteins within the Solute Carrier Family 2 (SLC2A), specifically encompassing the Class I (GLUT1-4) and Class III (GLUT6, 8, 10, 12, and 13) facilitated glucose transporters (Mueckler & Thorens, 2013). These transporters are essential for the movement of glucose, fructose, and other hexoses across cellular membranes, following a concentration gradient. Class I members like GLUT1 and GLUT3 are critical for basal glucose uptake in the brain and erythrocytes, while GLUT4 is the primary insulin-responsive transporter in muscle and adipose tissue (Thorens & Mueckler, 2010). Class III members are less characterized but are implicated in metabolic regulation and are often overexpressed in various malignancies to support the high glycolytic demands of cancer cells (Szablewski, 2013). Pharmacologically, these transporters are targeted by broad-spectrum inhibitors like Phloretin and Cytochalasin B, as well as certain HIV protease inhibitors like Ritonavir, which can cause off-target metabolic side effects (Hruz, 2011). Because of their diverse tissue distribution and vital roles in systemic glucose homeostasis, non-selective modulation of these transporters poses significant safety risks, including hypoglycemia and insulin resistance.
Inhibition of facilitated glucose transport across the plasma membrane
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