Insulin activation of brain Na(+)-K(+)-ATPase is mediated by alpha 2-form of enzyme

The sensitivity of the synaptosomal Na(+)-K(+)-ATPase to insulin was examined and found to be stimulated by the hormone when physiological intracellular sodium concentrations were present. Activation was not mediated by a sodium influx into the vesicles, as shown using sodium uptake experiments and by the fact that tetrodotoxin did not inhibit insulin action. Because the brain Na(+)-K(+)-ATPase catalytic subunit exists as two forms with different affinities for the inhibitory cardiac glycoside ouabain, the sensitivity of each form for insulin was examined. As previously observed in adipocytes, only the high-affinity component, alpha 2, was insulin sensitive. A dose-response curve of insulin activation of the Na(+)-K(+)-ATPase demonstrated a maximal insulin effect at relatively high hormone concentrations. It is unknown, therefore, whether stimulation of the brain Na(+)-K(+)-ATPase occurs in vivo.