Interactions of Ca2+, Mg2+, and Na+ in regulation of insulin release from rat islets.

Abstract

The effects of glucose and ionic modifications on unidirectional Ca2+ efflux and insulin release has been studied. Rat pancreatic islets were isotopically equilibrated with 45Ca2+ for 2 days and then perifused at 10(-8) M Ca2+ to allow for strict interpretation of 45Ca2+ efflux. Under these conditions 16.7 mM glucose inhibited Ca2+ efflux but did not stimulate insulin release. Removal of Mg2+ from the buffer markedly stimulated Ca2+ efflux that was counteracted by glucose. The omission of Na+ decreased basal Ca2+ efflux by 30% at 10(-8) M Ca2+, thus demonstrating the importance of Na-Ca countertransport for Ca2+ extrusion. Like glucose, Na+ omission or the addition of ouabain attenuated Ca2+ efflux stimulated by Mg2+ removal. Glucose may interfere with Na-Ca countertransport because the actions of 16.7 mM glucose and Na+ omission were not additive. At 10(-8) M Ca2+, glucose elicited insulin release only when both 1) loss of cellular calcium was minimized by prior inhibition of Ca2+ efflux (Na+ omission or ouabain), and 2) Ca2+ mobilization was favored by Mg2+ removal. Under these conditions (in contrast to normal Ca2+), insulin release was not accompanied by increased Ca2+ efflux. Thus, unidirectional Ca2+ measurements do not permit the detection of Ca2+ mobilization in intact islets because glucose may concomitantly inhibit Ca2+ extrusion.