Cell volume and the metabolic actions of insulin.

Insulin increases the volume of isolated hepatocytes and cells in perfused livers, but effects of the hormone on the volume of fat or muscle cells have not been demonstrated. Exogenous amino acids may stimulate swelling of liver cells and induce insulin-like effects on hepatic protein metabolism; however, swelling of liver cells can be induced by some treatment that do not induce insulin-like metabolic responses. Exogenous amino acids also influence protein metabolism of fat and muscle cells, but no relationship with cell volume has been established and no corresponding effects on metabolism of carbohydrates or lipids have been observed. Three families of mitogen-activated protein kinases are activated after changes in extracellular osmolarity but they appear to play little or no role in the metabolic actions of insulin. Direct evidence against a metabolic role for the extracellular signal-regulated kinases ERK-1 and ERK-2 is discussed. The c-Jun N-terminal kinases (also called stress-activated protein kinases) and the mammalian homologs of the yeast Hog protein kinase are strongly activated by environmental stresses associated with catabolic metabolism. We conclude that cell volume and protein metabolism may be correlated in liver but there is no compelling evidence that the effects of insulin on metabolism of liver, fat, or muscle cells can be accounted for by changes in cell volume. The effects of insulin on cell volume may represent a discrete aspect of the complete physiological response rather than an obligatory intermediate step in metabolic signalling.