Insulin release and phosphate ion efflux from rat pancreatic islets induced by L-leucine and its nonmetabolizable analogue, 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid.
When isolated rat pancreatic islets that had been labeled with 32P were exposed to 10mM L-leucine in a microperifusion system, there was a transitory, immediate heightened efflux of [32P]phosphate ions. Commencement of the phosphate flush coincided with the first release of insulin, and it occurred in the absence or presence of nonstimulatory levels of glucose (0.5 mg/ml). The effects of leucine upon phosphate efflux were not inhibited by D-mannoheptulose, whereas glucose-induced stimulations were suppressed. The phosphate flush could be induced also by the nonmetabolizable analogue of leucine, 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid. Like insulin release, the effect was stereospecific, with only one of the four stereoisomers, (-)-b-aminobicycloheptane carboxylic acid, being active. Analogue-induced phosphate and insulin release were totally suppressed in a medium containing D2O, but on reversion to H2O the efflux of both hormone and anion occured. It is concluded that insulin secretion from islet beta cells and the release of phosphate ions showed the same specificity for nutrient secretagogues and that both can be triggered even in the absence of exogenous oxidizable fuels. However, the partial dissociation of the dose-response curves for the two phenomena lends support to the contention that the phosphate flush reflects an earlier event in the sequence of stimulus-secretion coupling.
D000596:Amino Acids / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds; D003903:Deuterium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007930:Leucine / Q000494:pharmacology*; D008356:Mannoheptulose / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D013237:Stereoisomerism
D000596:Amino Acids; D001643:Bridged Bicyclo Compounds; D007328:Insulin; D010710:Phosphates; D008356:Mannoheptulose; D003903:Deuterium; D007930:Leucine