Practice question

GLUT family encoded by SLC2A genes includes fourteen isoforms differing in distribution, affinity and regulation. GLUT4 product of SLC2A4 stands out as only major isoform acutely dependent on insulin via regulated exocytosis. It contains twelve transmembrane helices forming MFS fold with central glucose cavity. Basally most protein sequestered in perinuclear storage vesicles associated with TUG and VAMP2 retained by AS160 GAP keeping Rab proteins GDP-bound. Insulin activates receptor tyrosine kinase, IRS1 phosphorylation, PI3K producing PIP3, recruiting Akt2 which phosphorylates TBC1D1 and TBC1D4 relieving Rab8A, Rab10, Rab14 to GTP driving vesicle translocation, docking via exocyst and fusion via syntaxin4 SNAP23. Exercise also triggers translocation via AMPK and calcium CaMKK independent of insulin. Once inserted, GLUT4 transports glucose by facilitated diffusion Km around 5 mM matching plasma glucose, enabling rapid postprandial uptake into muscle and adipose for glycogen and triglyceride formation, crucial for glucose homeostasis and postmeal glycemic control impaired in diabetes.