DIFFERENTIAL INSULIN SECRETORY RESPONSES TO CATIONIC AND BRANCHED-CHAIN AMINO-ACIDS

The long-term effects on the dynamics of glucose stimulated insulin re lease by the cationic amino acids arginine and lysine and the branched -chain amino acid leucine were examined. The rat pancreas perfusion mo del was utilized and particular emphasis was placed on modulation of t he glucose-stimulated synthesis-secretion coupling second phase. In th e presence of 16.7 mM glucose, 20 mM arginine, lysine, and leucine eac h potentiated first-phase insulin release by -50%, compared to glucose -only controls. Conversely, in the presence of 16.7 mM glucose, 20 mM arginine resulted in a 50% inhibition of second-phase (min 30-120) ins ulin release compared to glucose-only controls. Similarly, 20 mM lysin e in the presence of 16.7 mM glucose also caused a comparable inhibiti on of second-phase insulin release. Paradoxically, 20 mM leucine in th e presence of glucose had no significant inhibitory effect on second-p hase glucose-stimulated insulin release. The data suggest that these a mino acids mediate their effects on first- and second-phase insulin re lease via different mechanisms of action, which may reflect difference s and similarities in charge and/or metabolic fates within the beta ce ll. The data do not support the hypothesis that cationic charge is sol ely involved in the stimulus-secretion component, since all three amin o acids caused comparable potentiation of first-phase insulin release. Conversely, the inhibitory component of the second secretory phase ma y be mediated via a common charge-related metabolic pathway in the syn thesis-secretion coupling mechanism, since only the cationic amino aci ds inhibit this component, whereas leucine has no such effect.