Calcium and pancreatic beta-cell function. I. Stimulatory effects of pentobarbital on insulin release.
Islets microdissected from ob/ob-mice were exposed to 3mM pentobarbital in media which were normal or deficient in Ca2+. This treatment resulted in marked decrease of the islet content of cyclic AMP recorded in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Pentobarbital had a dual effect on insulin release. In addition to being a potent inhibitor of glucose-stimulated insulin release in media containing 2.56 mM Ca2+ it increased the amounts of insulin released in high glucose media deficient in Ca2+. There was a transient stimulation with ordinary concentrations of Ca2+ and 3mM glucose whtn the media also contained 3-isobutyl-1-methylxanthine. The stimulatory effect of pentobarbital persisted after replacing part of the Ca2+ in the beta-cell membrane with lanthanum ions and it could not be mimicked by lowering the oxygen tension of the incubation medium. It is suggested that pentobarbital stimulation of insulin release is the result of a specific action of the drug on the distribution of Ca2+ within the pancreatic beta-cells.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008820:Mice, Obese; D010424:Pentobarbital / Q000494:pharmacology*; D010477:Perfusion; D010726:Phosphodiesterase Inhibitors; D014970:Xanthines / Q000494:pharmacology
D007328:Insulin; D010726:Phosphodiesterase Inhibitors; D014970:Xanthines; D000242:Cyclic AMP; D010424:Pentobarbital; D005947:Glucose; D002118:Calcium