Stimulus-secretion coupling of amino acid-induced insulin release VII. The B-cell memory for L-glutamine

In the absence of another exogenous nutrient, L-glutamine does not stimulate insulin release from rat pancreatic islets or isolated perfused pancreases. L-glutamine, however, augments insulin release evoked by L-leucine. These two amino acids could interact by providing both the substrate (L-glutamate) and an activator (L-leucine) for the reaction catalyzed by glutamate dehydrogenase. Under suitable experimental conditions, as little as 0.5 mM L-glutamine is sufficient to enhance leucine-stimulated insulin release. When the pancreases or islets are first exposed to L-glutamine and then stimulated with L-leucine, the rate of secretion is much higher than that evoked by L-leucine in tissue not first exposed to L-glutamine. The memory of a prior exposure to L-glutamine persists for at least 25 min after removal of the latter amino acid from the extracellular fluid. This memory phenomenon is not dependent on the presence of Ca2+ in the extracellular fluid during the first exposure to L-glutamine, but is suppressed when such a prior exposure is performed in the absence of extracellular K+. The memory phenomenon could be due, in part at least, to inhibition by L-glutamine of K+ conductance in the B-cell plasma membrane. Moreover, the amount of L-glutamate which accumulates in islets exposed to L-glutamine is sufficient to maintain, for a much longer period than with other nutrient secretagogues, a sustained increase in catabolic fluxes after removal of the amino acid from the extracellular fluid.