The Stimulus-Secretion Coupling of Amino Acid-induced Insulin Release: Secretory and Oxidative Response of Pancreatic Islets to L-Asparagine

L-Asparagine (2–10 mM) failed to affect insulin secretion from rat pancreatic islets incubated in the absence of exogenous nutrient or presence of D-glucose, but caused a dose-related and progressive enhancement of insulin release evoked by L-leucine, 2-aminobicyclo [2,2,1] heptane-2-carboxylate, or 2-ketoisocaproate. The secretory response to the combination of L-asparagine and L-leucine was augmented by theophylline and inhibited in the absence of extracellular Ca²⁺ or presence of either menadione or methylamine. L-Asparagine augmented leucine-stimulated ⁴⁵Ca net uptake. The ATP content, rate of O₂ uptake, and malate/ pyruvate ratio were not significantly different in islets exposed to L-leucine alone or to both L-asparagine and L-leucine, respectively. In the sole presence of L-asparagine, however, the malate/oxalacetate ratio was decreased and the malat/pyruvate ratio increased, relative to basal values. It is proposed that the enhancing action of L-asparagine upon insulin release evoked by L-leucine might be due to an accelerated generation rate of cytosolic NAOPH, rather than to any sizable increase in either islet respiration or steady-state cytosolic NADPH/NADP⁺ ratio.