T he effects of somatostatin and epinephrine have been studied with regard to glucose-induced insulin release and ⁴⁵Ca⁺⁺ uptake by rat pancreatic islets after 2 days in tissue culture and with regard to ⁴⁵Ca⁺⁺ efflux from islets loaded with the radio-isotope during the 2 days of culture. ⁴⁵Ca⁺⁺ uptake, measured simultaneously with insulin release, was linear with time for 5 min. ⁴⁵Ca⁺⁺ efflux and insulin release were also measured simultaneously from perifused islets.Glucose (16.7 mM) markedly stimulated insulin release and ⁴⁵Ca⁺⁺ uptake. Somatostatin inhibited the stimulation of insulin release by glucose in a concentration-related manner (1-1,000 ng/ml) but was without effect on the glucose-induced stimulation of ⁴⁵Ca⁺⁺ uptake. Similarly, under perifusion conditions, both phases of insulin release were inhibited by somatostatin while no effect was observed on the pattern of ⁴⁵Ca⁺⁺ efflux after glucose.Epinephrine, in contrast to somatostatin, caused a concentration-dependent inhibition of the stimulation of both insulin release and ⁴⁵Ca⁺⁺ uptake by glucose. Both phases of insulin release were inhibited by epinephrine and marked inhibition could be observed with no change in the characteristic glucose-evoked pattern of ⁴⁵Ca⁺⁺ efflux (e.g., with 10 nM epinephrine). The inhibitory effect of epinephrine on ⁴⁵Ca⁺⁺ uptake and insulin release appeared to be mediated via an α-adrenergic mechanism, since is was abolished in the presence of phentolamine.Somatostatin inhibits insulin release without any detectable effect upon the handling of calcium by the islets. In contrast, inhibition of insulin release by epinephrine is accompanied by a partial inhibition of glucose-induced Ca⁺⁺ uptake.