GLUT4

GLUT4 is the principal insulin-responsive glucose transporter mediating glucose uptake in skeletal muscle and adipose tissue, thereby supporting whole-body glucose homeostasis^[1]. Mechanistically, insulin increases glucose uptake by regulating the trafficking of GLUT4-containing vesicles to the plasma membrane through insulin signaling, including PI3K/Akt-linked processes^[2][3]. This trafficking process matters for metabolic disease because impaired insulin-stimulated GLUT4 translocation in muscle and adipose tissue underlies insulin resistance, a major risk factor for type 2 diabetes and other metabolic disorders^[3][4]. In disease models, GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes, supporting the experimental value of GLUT4 expression and trafficking models^[5]. Compared with related isoforms, GLUT4 differs from GLUT1 because its intracellular targeting is isoform specific, and GLUT1 and GLUT4 contain sequence information that directs them to distinct cellular compartments^[6][7]. For research applications, human GLUT4 structural analysis with cytochalasin B and endogenous GLUT4 translocation assays provide tools for studying transporter inhibition, trafficking regulation, and insulin resistance in cell models^[8][9]. WZB117 also inhibits insulin-regulated GLUT4 more potently than GLUT1 or GLUT3, making isoform selectivity an important variable in inhibitor-based study design^[10].