2.A.1.1.80
Insulin-responsive facilitative glucose transporter in skeletal and cardiac muscle, adipose, and other tissues, Glut4 (GTR4; SLC2A4; 509aas). Defects in Glut4 cause noninsulin-dependent diabetes mellitus (NIDDM). Hyperinsulinemia leads to uncoupled insulin regulation of the GLUT4 glucose transporter and the FoxO1 transcription factor (Gonzalez et al., 2011). The first luminal loop confers insulin responsiveness to GLUT4 (Kim and Kandror, 2012). Exercise increases Glut4 synthesis in a process involving several protein kinases, the Glut4 enhancer factor (GEF; SLC2A4 regulator; Q9NR83), and the myocyte enhancing factor 2 (MEF2; NP_001139257). (McGee and Hargreaves 2006; Wright 2007; Zorzano et al. 2005). monoclonal antibodies against the GLUT4 inward-open and outward-open states have been isoated (Tucker et al. 2018). It is phosphoryated by protein kinase C-β, PRKCB or PKCB (Lee et al. 2015). Insulin-induced GLUT4 transport is observed in the heart and brain in addition to the skeletal muscle and adipocytes, and hormones other than insulin can enhance GLUT4 transport (Wang et al. 2020). Prolonged preoperative fasting induces postoperative insulin resistance by ER-stress mediated Glut4 down-regulation in skeletal muscle (Lin et al. 2021). GLUT4 is the primary glucose transporter in adipose and skeletal muscle tissues, and its cellular trafficking is regulated by insulin signaling. Failed or reduced plasma membrane localization of GLUT4 is associated with diabetes. The cryo-EM structures of human GLUT4 bound to a small molecule inhibitor cytochalasin B (CCB) at resolutions of 3.3 Å which exhibits an inward-open conformation. The cryo-EM structure reveals an extracellular glycosylation site and an intracellular helix that is invisible in the crystal structure of GLUT1 (Yuan et al. 2022). Tectorigenin targets PKACα to promote GLUT4 expression in skeletal muscle and improve insulin resistance in vitro and in vivo (Yao et al. 2023). Key molecular players in insulin resistance (IR) are the insulin receptor and glucose transporter 4, and certain natural products, such as lipids, phenols, terpenes, antibiotics and alkaloids have beneficial effects on IR which are named "membrane-active immunomodulators" (MAIMs) (Izbicka and Streeper 2023). An example is the medium chain fatty acid ester diethyl azelate (DEA), which increases the fluidity of plasma membranes with subsequent downstream effects on cellular signaling and improves the symptoms of IR. The intracellular helical bundle of human glucose transporter GLUT4 is important for complex formation with ASP (Huang et al. 2023). Diabetes-induced electrophysiological alterations on neurosomes in ganglia of the peripheral nervous system have been reported (Leal-Cardoso et al. 2023). Regulated dynamic subcellular GLUT4 localization has been revealed by proximal proteome mapping in human muscle cells (Ray et al. 2023). In goats, this system is closely associate with lipid metabolism (Zhang et al. 2024).  New compounds lowered the systolic blood pressure (from 149 to 120 mmHg), but only LQM312 and LQM319 improved the metabolic state of hypoxic cardiomyocytes mediated by GLUT1 and GLUT4 (Hernández-Serda et al. 2024). In silico studies suggested that Captopril and LQM312 mimic the interaction with the AMPK γ-subunit. Therefore, these compounds could activate AMPK, promoting the GLUT4 trafficking signaling pathway (Hernández-Serda et al. 2024). Indian lychee honey ameliorates hepatic glucose uptake by regulating the ChREBP/Glut4 axis under insulin-resistant conditions (Ghosh et al. 2025).