Cell volume plays a decisive role in the regulation of hepatic metabolism. The present study has been performed to test for an effect of insulin and glucagon on liver cell volume. To this end, the effect of these hormones has been studied in isolated perfused rat livers and isolated rat hepatocytes. Insulin leads to rapid stimulation of cellular K+ uptake and increase of cell volume, effects reversed by glucagon or cAMP. The insulin stimulated cellular K+ uptake is significantly decreased in the presence of either loop diuretics (furosemide or bumetanide) or amiloride and is completely inhibited in the presence of both, bumetanide and amiloride. The glucagon stimulated cellular K+ release in the presence of insulin is blunted by K+ channel blocker quinidine. The effects of insulin and glucagon on liver cell volume could participate in the regulation of hepatic metabolism by these hormones.

In single pass perfused rat liver, rapid osmotic water shifts across the plasma membrane in response to hyperosmolar urea were followed by monitoring liver mass and transient concentrating or diluting effects on Na* concentration in effluent perfusate. Sudden addition or removal of hyperosmolar urea (200 mM, resulting in a step change of the perfusate osmolarity from 305 to 505 mosmol/l) had little effect on liver mass or Na* activity in the effluent perfusate, suggesting that urea equilibrated at a rate similar to that of water across the liver plasma membrane. When, however, phloretin (0.2 mM) was present, sudden addition ( The data indicate that urea export across the hepatocyte plasma membrane is almost as fast as water export. The urea transport mechanism is sensitive to phloretin and other phenol compounds, works with high capacity and is distinct from the water-transporting system. The regulation of this putative transport mechanism and its relevance for hepatic nitrogen metabolism remain to be established.