Mechanisms and consequences of Na+,K+-pump regulation by insulin and leptin.
Hormonal control of the Na+,K+-pump modulates membrane potential in mammalian cells, which in turn drives ion coupled transport processes and maintains cell volume and osmotic balance. Na+,K+-pump regulation is particularly important in the musculoskeletal, cardiovascular and renal systems. Decreased Na+,K+-pump activity can result in a rise in intracellular Na+ concentrations which in turn increase Na+/Ca2+ exchange, thereby raising intracellular Ca2+ levels. In cardiac and skeletal muscle, this could interfere with normal contractile activity. Similarly, in vascular smooth muscle the result would be resistance to vasodilation. Inhibition of the Na+,K+-pump can also reduce the driving force for renal tubular Na+ reabsorption, elevating Na+ excretion. By virtue of decreasing the membrane potential, thus allowing more efficient depolarization of nerve endings and by increasing intracellular Ca2+, inhibition of the Na+,K+-pump can increase nervous tone. The ability of insulin to stimulate the Na+,K+-pump in various cells and tissues, and the physiological significance thereof, have been well documented. Much less is known about the effect of leptin on the Na+,K+-pump. We have shown that leptin inhibits Na+,K+-pump function in 3T3-L1 fibroblasts. Defects in insulin and leptin action are associated with diabetes and obesity, respectively, both of which are commonly associated with cardiovascular complications. In this review we discuss the mechanisms of Na+,K+-pump regulation by insulin and leptin and highlight how, when they fail, they may contribute to the pathophysiology of hypertension associated with diabetes and obesity.
Sweeney
G
G
Programme in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Klip
A
A
D016475:3T3 Cells; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D020738:Leptin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007328:Insulin; D020738:Leptin; D000254:Sodium-Potassium-Exchanging ATPase