LAUSR

In this study, we investigated the role of calcium/calmodulin‐dependent protein kinase II (CaMKII) in contraction‐stimulated glucose uptake in skeletal muscle. C2C12 myotubes were contracted by electrical pulse stimulation (EPS), and treadmill running was used to exercise mice. The activities of CaMKII, the small G protein Rac1, and the Rac1 effector kinase PAK1 were elevated in muscle by running exercise or EPS, while they were lowered by the CaMKII inhibitor KN‐93 and/or small interfering RNA (siRNA)‐mediated knockdown. EPS induced the mRNA and protein expression of the Rac1‐GEF Kalirin in a CaMKII‐dependent manner. EPS‐induced Rac1 activation was lowered by the Kalirin inhibitor ITX3 or siRNA‐mediated Kalirin knockdown. KN‐93, ITX3, and siRNA‐mediated Kalirin knockdown reduced EPS‐induced glucose uptake. These findings define a CaMKII‐Kalirin‐Rac1 signaling pathway that contributes to contraction‐stimulated glucose uptake in skeletal muscle myotubes and tissue.