Rac1 Is a Novel Regulator of Contraction-Stimulated Glucose Uptake in Skeletal Muscle

In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates contraction-induced glucose uptake is unknown. Therefore, we studied the effects of in vivo exercise and ex vivo muscle contractions on Rac1 signaling and its regulatory role in glucose uptake in mice and humans. Muscle Rac1-GTP binding was increased after exercise in mice (;60–100%) and humans (;40%), and this acti-vation was AMP-activated protein kinase independent. Rac1 in-hibition reduced contraction-stimulated glucose uptake in mouse muscle by 55 % in soleus and by 20–58 % in extensor digitorum longus (EDL; P, 0.01). In agreement, the contraction-stimulated increment in glucose uptake was decreased by 27 % (P = 0.1) an