Cell Volume, the Serum and Glucocorticoid Inducible Kinase 1 and the Liver

In virtually all cells including hepatocytes cell volume regulation is accomplished during cell swelling by cellular ion release (activation of K+ channels and/or anion channels, KCl-cotransport, parallel activation of K+/H+ exchange and Cl-/HCO3- exchange) and following cell shrinkage by cellular ion uptake (activation of Na+, K+, 2Cl(-) cotransport, Na+/H+ exchange in parallel to Cl-/HCO3- exchange and Na+-channels). Moreover, cell shrinkage triggers the cellular accumulation of organic osmolytes (e.g., myoinositol, betaine, phosphorylcholine, taurine). Cell volume is a powerful regulator of hepatic metabolism. Cell shrinkage stimulates and cell swelling inhibits proteolysis and glycogenolysis. Moreover, cell volume influences the generation of and sensitivity to oxidants. Cell volume regulatory mechanisms furthermore do play a role in fibrosing disease. Kinases stimulating cell volume regulatory mechanisms include the serum and glucocorticoid inducible kinase SGK1, which is expressed in the liver, is genomically up-regulated by cell shrinkage, stimulates a wide variety of channels and transporters including Na+, K+, 2Cl(-) cotransport and Na+/H+ exchange and is known to participate in the stimulation of fibrosis. Accordingly, excessive SGK1 expression is observed in liver cirrhosis. The case is made that SGK1 participates in the regulation of liver cell volume and thus in the regulation of hepatic metabolism.