Cell Volume – A ‘Second Messenger’ in the Regulation of Metabolism by Amino Acids and Hormones

Abstract

Alterations in cell volume markedly influence hepatic metabolism and play a key role in the regulation of cellular metabolism by amino acids and hormones. A variety of amino acids swell cells by concentrative uptake via Na⁺-coupled transport, insulin swells cells by stimulation of Na⁺-K⁺-2C1^- cotransport and Na⁺/H⁺ exchange, and glucagon shrinks cells at least in part by stimulating cellular potassium loss through K⁺ channels. The alterations in cell volume, in turn, profoundly modify cellular metabolism. For instance, hepatic proteolysis is stimulated by cell shrinkage and inhibited by cell swelling. The effects of some amino acids, of insulin and of glucagon on hepatic proteolysis are fully accounted for by their influence on cell volume. Moreover, the amino-acid- and hormone-induced changes in proteolysis are abolished if the respective alterations in cell volume are avoided. Thus, cell volume serves as a ‘second messenger’ mediating the regulation of metabolism. The ‘third messenger’, i.e. the mechanism linking cell volume changes to cell metabolism, however, is still elusive.