Modifying actions of calcium ionophores on insulin release.
Beta-Cell-rich pancreatic islets were microdissected from noninbred ob/obmice and exposed to the calcium ionophores X-537A and A-23187. X-537A differed from A-23187 in being a potent insulin secretagogue at non-stimulating glucose concentrations. Both ionophores inhibited the stimulation of insulin release obtained after adding 20 mM glucose to the incubation medium. The latter observation is consistent with the idea of a reduced beta-cell function when the Ca-2+ in the functionally important intracellular pool (s) exceeds a certain concentration. The ionophore inhibition of the glucose-stimulated insulin release may at least in part result from decreased formation of cyclic AMP, since X-537A proved to be as effective as L-epinephrine in reducing the islet content of this nucleotide in the presence of a phosphodiesterase inhibitor. The secretagogic action of X-537A at a low glucose concentration persisted when different ions were omitted from the incubation medium and was actually considerably enhanced in the absence of extracellular Ca-2+. The insulin-releasing action of X-537A was neither influenced by 3-O-methyglucose nor by drugs blocking the alpha or beta-adrenergic receptor sites. Exposure of the pancreatic beta-cells to metabolic inhibitors in concentrations which significantly reduced the secretory response to glucose, potentiated stimulation of insulin release by X-537A, suggesting that this effect may in part be accounted for by intracellular dissolution of secretory granules.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000968:Antimycin A / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D005985:Glyceraldehyde / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007460:Iodoacetamide / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007832:Lasalocid / Q000494:pharmacology; D008757:Methylglucosides / Q000494:pharmacology; D051379:Mice; D008820:Mice, Obese; D009570:Nitriles / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology; D010477:Perfusion; D010643:Phenoxybenzamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013267:Stilbenes / Q000494:pharmacology; D013997:Time Factors
D000900:Anti-Bacterial Agents; D003470:Culture Media; D007328:Insulin; D008757:Methylglucosides; D009570:Nitriles; D009942:Organometallic Compounds; D013267:Stilbenes; D010643:Phenoxybenzamine; D005985:Glyceraldehyde; D000001:Calcimycin; D000968:Antimycin A; D011433:Propranolol; D000242:Cyclic AMP; D005947:Glucose; D002118:Calcium; D007832:Lasalocid; D004837:Epinephrine; D007460:Iodoacetamide