The stimulus-secretion coupling of amino acid-induced insulin release.

L-glutamine dramatically augments insulin release evoked by L-leucine. The dynamics, specificity and environmental modifications of the insulin secretory response to the combination of L-glutamine and L-leucine were investigated. L-glutamine alone failed to stimulate proinsulin biosynthesis or insulin release in rat pancreatic islets, but augmented synthesis and secretion evoked by L-leucine. In relation to the secretory response, L-glutamine could be replaced by L-asparagine but not L-glutamate; L-leucine could be replaced by L-norvaline or L-isoleucine but not by L-valine, L-norleucine, glycine, L-serine, L-lysine, L-phenylalanine or L-arginine. The secretory response to L-leucine was rapid and biphasic, whereas the enhancing action of L-glutamine upon insulin release was progressive. The release of insulin evoked by the combination of L-leucine and L-glutamine was inhibited by antimycin A, menadione, ammonium ions, verapamil, adrenaline, and by the absence of extracellular Ca. It was increased at high carbon dioxide tension, and by glucose, theophylline and cytochalasin B. It is concluded that the enhancing action of L-glutamine upon insulin release evoked by certain amino acids represents a phenomenon dependent on the integrity of oxidative metabolism and involving essentially the same sequence of metabolic, ionic and motile events as that characterizing the process of glucose-induced insulin release. [ABSTRACT FROM AUTHOR]