Stimulation of insulin release in the absence of extracellular calcium by isobutylmethylxanthine and its inhibition by somatostatin

Abstract

It has been suggested that somatostatin may inhibit insulin release by interfering with pancreatic islet calcium uptake. To further investigate this hypothesis, the effect of somatostatin on insulin release was examined under conditions where islet uptake of calcium would be unlikely to occur. The phosphodiesterase inhibitor, isobutylmethylxanthine (0.75 mM), was found to stimulate biphasic insulin release from rat pancreases perfused in vitro in the absence of added extracellular calcium on a background of 0.3 mM EGTA And 8 mM glucose; these results support previous suggestions that methylxanthine phosphodiesterase inhibitors may stimulate insulin release by increasing islet cytosol free calcium through translocation of bound (stored) intraislet calcium. Somatostatin (1.0 muM) completely inhibited both phases of isobutylmethylxanthine-stimulated insulin release. Since uptake of extracellular calcium by islets was unlikely under the present experimental conditions, these results suggest that somatostatin inhibition of insulin release is probably due to interference with a cAMP-dependent translocation of intraislet calcium, or to interference with some other effects of cAMP or an effect of calcium itself rather than to interference with islet calcium uptake.