Calcium and pancreatic β-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 a 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 3 mM glucose when the media also contained 3-isobutyl-1-methylxanthine. The stimulatory effect of pentobarbital persisted after replacing part of the Ca²⁺ in the β-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 β-cells.