Differential insulin secretory responses to cationic and branched-chain amino acids.
The long-term effects on the dynamics of glucose-stimulated insulin release by the cationic amino acids arginine and lysine and the branched-chain amino acid leucine were examined. The rat pancreas perfusion model was utilized and particular emphasis was placed on modulation of the glucose-stimulated synthesis-secretion coupling second phase. In the presence of 16.7 mM glucose, 20 mM arginine, lysine, and leucine each potentiated first-phase insulin release by approximately 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) insulin release compared to glucose-only controls. Similarly, 20 mM lysine in the presence of 16.7 mM glucose also caused a comparable inhibition of second-phase insulin release. Paradoxically, 20 mM leucine in the presence of glucose had no significant inhibitory effect on second-phase glucose-stimulated insulin release. The data suggest that these amino acids mediate their effects on first- and second-phase insulin release via different mechanisms of action, which may reflect differences and similarities in charge and/or metabolic fates within the beta cell. The data do not support the hypothesis that cationic charge is solely involved in the stimulus-secretion component, since all three amino acids caused comparable potentiation of first-phase insulin release. Conversely, the inhibitory component of the second secretory phase may be mediated via a common charge-related metabolic pathway in the synthesis-secretion coupling mechanism, since only the cationic amino acids inhibit this component, whereas leucine has no such effect.
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, USA.
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D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007930:Leucine / Q000494:pharmacology*; D008239:Lysine / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010477:Perfusion; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D001120:Arginine; D007930:Leucine; D005947:Glucose; D008239:Lysine