Stimulus-secretion coupling of arginine-induced insulin release: comparison with lysine-induced insulin secretion

L-Lysine, like-L-arginine, L-ornithine, or L-homoarginine, accumulated in rat pancreatic islets and stimulated 86Rb efflux, 45Ca uptake and efflux, and insulin release in islets exposed to D-glucose (7.0 mM). The effect of L-lysine differed from that of the other cationic amino acids by such features as the absence of a threshold concentration for stimulation of insulin release, a much lesser sensitivity of the secretory response to intracellular acidification, and the stimulation of 86Rb net uptake over 60 min of incubation. This coincided with the fact that even in the absence of another exogenous nutrient, L-lysine was well oxidized, augmented NH4+ production, increased both the ATP content and ATP/ADP ratio, caused a time-related decrease in 86Rb fractional outflow, and provoked either a transient (10 mM L-lysine) or sustained (20 mM L-lysine) stimulation of insulin secretion. It is proposed, therefore, that the functional response of the pancreatic B-cell to L-lysine involves not only a biophysical mechanism similar to that responsible for the insulinotropic action of L-homoarginine, but also a significant, albeit modest, metabolic component, which reflects the capacity of L-lysine to act as a fuel in islet cells.