The Stimulus-Secretion Coupling of Amino Acid-Induced Insulin Release

Summary

L-Leucine and its nonmetabolized analog, 2-aminobicyclo-[2,2,1]heptane-2-carboxylic acid (BCH), do not act identically in pancreatic islets. For instance, BCH stimulates more markedly than leucine the output of ¹⁴CO₂ from islets prelabelled with L-[U-¹⁴C] glutamine. Although leucine and BCH stimulate insulin release to the same extent in the presence of glutamine, the rate of secretion is higher in leucine-stimulated than in BCH-stimulated islets when 2-ketoisocaproate is present in the incubation medium alone or together with glutamine. Such a difference in secretory rate coincides with contrasting effects of leucine and BCH, respectively, on both NH₄ ⁺ production and glutamine oxidation by the islets exposed to 2-keto-isocaproate. These differences are best explained by the unability of BCH, as distinct from leucine, to act as a transamination partner of 2-ketoglutarate, and emphasize the view that the secretory response to nutrients tightly depends on the regulation of catabolic events in the islet cells.

Key-Words:

Pancreatic Islets - Insulin Release - L-Leucine - b(±)2-Aminobicyclo[2,2,1]Heptane-2-Carboxylic Acid - L-Glutamine - 2-Ketoisocaproate