Abstract

Insulin-stimulated glucose uptake requires the activation of several signaling pathways to mediate the translocation and fusion of GLUT4 vesicles from an intracellular pool to the plasma membrane. Our previous studies demonstrated that GLUT4-mediated glucose uptake is a myosin II-dependent process in adipocytes. The studies presented here show that myosin IIA colocalizes with GLUT4 at the plasma membrane after insulin stimulation. We further show that insulin stimulates myosin IIA recruitment to the plasma membrane after GLUT4 vesicle translocation. We also show that myosin II activity is required for proper GLUT4 vesicle fusion at the plasma membrane. Based on our findings, we hypothesize that myosin II is activated upon insulin stimulation and recruited to the cell cortex to facilitate GLUT4 fusion with the plasma membrane. The identification of myosin IIA as a mediator of GLUT4-mediated glucose uptake represents an important advance in our understanding of the mechanisms regulating glucose homeostasis.

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