The stimulus-secretion coupling of amino acid-induced insulin release. Influence of a nonmetabolized analog of leucine on the metabolism of glutamine in pancreatic islets.
L-Glutamine causes a dose-related enhancement of insulin release evoked, in rat pancreatic islets, by the nonmetabolized analog of leucine, 2-aminobicyclo-[2,2,1]heptane-2-carboxylic acid (BCH). The influence of BCH upon the metabolism of L-glutamine was investigated. In the islets exposed to L-glutamine, BCH decreased the deamidation of glutamine, but stimulated the oxidative deamination of glutamate, increased the rate of generation and islet content of 2-ketoglutarate, and augmented the oxidation of L-[U-14C]glutamine. BCH antagonized the sparing action of L-glutamine upon the oxidation of endogenous fatty acids. The stimulation of insulin release by the association of L-glutamine and BCH was commensurate with the estimated increase in O2 consumption and coincided with an increase in the islet NADPH/NADP+ ratio, net uptake of 45Ca, and cyclic AMP concentration. It is concluded that insulin release evoked by these amino acids is causally linked to an increase in catabolic fluxes, the secretagogues acting in the islet cells as a fuel (glutamine) or enzyme activator (BCH).
D000227:Adenine Nucleotides / Q000378:metabolism; D000596:Amino Acids / Q000494:pharmacology*; D000598:Amino Acids, Cyclic; D000818:Animals; D005973:Glutamine / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats
D000227:Adenine Nucleotides; D000596:Amino Acids; D000598:Amino Acids, Cyclic; D007328:Insulin; D005973:Glutamine; D009243:NAD; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D009249:NADP