The stimulus-secretion coupling of amino acid-induced insulin release. II. Sensitivity to K+, NH4+ and H+ of leucine-stimulated islets.
The insulinotropic action of L-leucine is thought to be tightly coupled with the metabolism of this amino acid in pancreatic islet cells. Consistent with such a view, the removal of extracellular K+ severely impaired L-leucine deamination and oxidation and L-leucine-stimulated insulin release. L-leucine increased the NH4+ content of islet cells. Exogenous NH4+ inhibited more markedly 45Ca net uptake and insulin release in islets exposed to L-leucine than in islets stimulated by D-glucose, D-glyceraldehyde or alpha-ketoisocaproate, all nutrients being used at concentrations of equal insulinotropic capacity. The islets exposed to L-leucine also differed from those stimulated with D-glucose by a somewhat higher 45Ca net uptake relative to insulin output, and an increased secretory activity in response to extracellular or intracellular acidification. It is proposed that in the islets exposed to L-leucine, an alteration in the islet content of NH4+ and possibly H+ interferes with the normal coupling between metabolic and secretory events.
D000641:Ammonia / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007930:Leucine / Q000378:metabolism / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats
D007328:Insulin; D000641:Ammonia; D007930:Leucine; D011188:Potassium; D002118:Calcium