Osmosensing and signaling in the regulation of liver function

Whereas the kidney has to cope with extremely high osmolarity during urinary concentration the liver is exposed to only moderate alterations in ambient osmolarity. More importantly, hormones, amino acids, and oxidative stress induce hepatocyte swelling or shrinkage within a narrow physiological range. It is meanwhile well-acknowledged that volume changes in different cell types trigger signal transduction events which contribute to the control and regulation of metabolism, transport and gene expression. For example, hepatocyte swelling induced by either hypoosmolarity, glutamine, ethanol, or insulin via activation of the p38-type mitogen-activated protein (MAP)-kinase mediates inhibition of autophagic proteolysis in perfused rat liver. On the other hand, dehydration of hepatocytes as triggered by hyperosmolarity produces insulin- and cytokine resistance and sensitizes cells to apoptotic stimuli. The volume-sensitivity of cell function relies on osmosensing structures which stimulate signal transduction in response to cell volume changes. This article focuses on recent developments regarding the understanding of osmosensing and signaling in the liver and its pathophysiological impact.