Regulation of the Na+/K+-ATPase by insulin: why and how?
The sodium-potassium ATPase (Na+/K+-ATPase or Na+/K+-pump) is an enzyme present at the surface of all eukaryotic cells, which actively extrudes Na+ from cells in exchange for K+ at a ratio of 3:2, respectively. Its activity also provides the driving force for secondary active transport of solutes such as amino acids, phosphate, vitamins and, in epithelial cells, glucose. The enzyme consists of two subunits (alpha and beta) each expressed in several isoforms. Many hormones regulate Na+/K+-ATPase activity and in this review we will focus on the effects of insulin. The possible mechanisms whereby insulin controls Na+/K+-ATPase activity are discussed. These are tissue- and isoform-specific, and include reversible covalent modification of catalytic subunits, activation by a rise in intracellular Na+ concentration, altered Na+ sensitivity and changes in subunit gene or protein expression. Given the recent escalation in knowledge of insulin-stimulated signal transduction systems, it is pertinent to ask which intracellular signalling pathways are utilized by insulin in controlling Na+/K+-ATPase activity. Evidence for and against a role for the phosphatidylinositol-3-kinase and mitogen activated protein kinase arms of the insulin-stimulated intracellular signalling networks is suggested. Finally, the clinical relevance of Na+/K+-ATPase control by insulin in diabetes and related disorders is addressed.
Sweeney
G
G
Division of Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Klip
A
A
D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000502:physiology*; D008954:Models, Biological; D009928:Organ Specificity; D015398:Signal Transduction / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology
D007328:Insulin; D000254:Sodium-Potassium-Exchanging ATPase