Narrative review uncovers molecular pathways regulating GLUT4 translocation and expression in skeletal muscle, highlighting mechanisms that enhance insulin sensitivity after exercise.
Key Points
To review the signaling cascades and molecular mechanisms that regulate contraction-stimulated GLUT4 translocation and exercise-induced GLUT4 gene expression in skeletal muscle.
Synthesized molecular evidence on proximal and distal signaling networks governing muscle glucose uptake during acute contraction.
Evaluated transcriptional pathways, chromatin modifications, and kinase cascades that control long-term GLUT4 expression following exercise training.
Acute muscle contraction mobilizes GLUT4 from intracellular depots to the plasma membrane through proximal mediators (AMPK, Ca2+, NOS) and distal trafficking machinery (GTPases, Rab, and SNARE proteins).
Exercise training acts as the most potent stimulus for GLUT4 expression via an AMPK- and CaMKII-dependent pathway, causing HDAC4/5 nuclear export, MEF2 activation, and promoter hyperacetylation to enhance insulin action and glycogen storage.