The stimulus-secretion coupling of amino acid-induced insulin release. XII. Contrasting effects of L-leucine and a nonmetabolized analog upon islet metabolism and insulin secretion.
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 14 CO2 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 inability 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.
D000596:Amino Acids / Q000494:pharmacology*; D000598:Amino Acids, Cyclic; D000818:Animals; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007930:Leucine / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D005971:Glutamates; D007328:Insulin; D005973:Glutamine; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D018698:Glutamic Acid; D007930:Leucine