Solute carrier family 2, facilitated glucose transporter member 4 (GLUT4)

Solute carrier family 2, facilitated glucose transporter member 4 (GLUT4) is the primary insulin-regulated glucose transporter in mammals, predominantly expressed in skeletal muscle, adipose tissue, and cardiac muscle (UniProt, 2024; StatPearls, 2023). Unlike other members of the GLUT family, GLUT4 is uniquely stored in intracellular vesicles and only translocates to the plasma membrane in response to specific stimuli such as insulin or physical exercise (Wikipedia, 2024; PMC, 2019). This regulated movement is essential for maintaining systemic glucose homeostasis by allowing cells to rapidly increase glucose uptake from the bloodstream following a meal or during energy expenditure (MDPI, 2022). Dysfunction in GLUT4 expression or its trafficking mechanism is a hallmark of insulin resistance and is central to the pathogenesis of type 2 diabetes mellitus and metabolic syndrome (NCBI Gene, 2024; MDPI, 2024). Therapeutic strategies often focus on enhancing GLUT4 translocation or expression, as seen with drugs like thiazolidinediones and metformin, to improve insulin sensitivity (StatPearls, 2023; Patsnap, 2024). Conversely, certain medications, such as HIV protease inhibitors, can inadvertently inhibit GLUT4, leading to adverse metabolic effects like hyperglycemia and lipodystrophy (MDPI, 2022; ResearchGate, 2025).

Other names

Glucose transporter type 4, insulin-responsiveSLC2A4GLUT-4Insulin-responsive glucose transporter type 4

GLUT4 facilitates the ATP-independent diffusion of glucose across the plasma membrane down its concentration gradient (StatPearls, 2023). In the basal state, approximately 90% of GLUT4 is sequestered within specialized intracellular compartments called GLUT4 storage vesicles (GSVs) (Wikipedia, 2024; MDPI, 2024). Upon insulin stimulation or muscle contraction, signaling cascades involving PI3K/Akt or AMPK pathways trigger the translocation of these vesicles to the cell surface, where they fuse with the plasma membrane to increase glucose uptake (Cell Metabolism, 2007; PMC, 2019).