Regulatory effect of insulin on the structure, function and metabolism of Na(+)/K(+)-ATPase (Review)

Na(+)/K(+)-ATPase is an ancient enzyme, the role of which is to maintain Na(+) and K(+) gradients across cell membranes, thus preserving intracellular ion homeostasis. The regulation of Na(+)/K(+)-ATPase is affected by several regulatory factors through a number of pathways, with hormones serving important short-term and long-term regulatory functions. Na(+)/K(+)-ATPase can also be degraded through activation of the ubiquitin proteasome and autophagy-lysosomal pathways, thereby affecting its abundance and enzymatic activity. As regards the regulatory effect of insulin, it has been found to upregulate the relative abundance of Na(+)/K(+)-ATPase and restore the transport efficiency in multiple in vitro and in vivo experiments. Therefore, elucidating the role of insulin in the regulation Na(+)/K(+)-ATPase may help uncover new drug targets for the treatment of related diseases. The aim of the present study was to review the structure and function of Na(+)/K(+)-ATPase and to discuss the possible mechanisms through which it may be regulated by insulin, in order to investigate the possibility of designing new therapies for related diseases.