Figure 9. Schematic depiction of heterotypic endosomal fusion induced by insulin in skeletal myofibres.

Comprehensive imaging analyses of GLUT4 behaviour in skeletal muscle revealed that insulin triggers acute heterotypic endomembrane fusion of GLUT4‐containing vesicles with a subset of TfR‐containing endosomes. The insulin‐responsive actions exerted on small GLUT4‐containing vesicles are enhanced after exercise‐mimetic stimuli, possibly regulated by functional co‐operation between AS160 and Tbc1d1. The findings provide a conceptual framework indicating that GLUT4 ‘protein’ trafficking via heterotypic fusion is a critical feature of GLUT4 translocation in skeletal muscles and also suggest that the insulin‐responsive efficacy of the endomembranous fusion process is involved in the benefits of exercise.