AJP - Endocrinology and Metabolism, Vol 244, Issue 3 222-E229, Copyright © 1983 by American Physiological Society
Interactions of Ca2+, Mg2+, and Na+ in regulation of insulin release from rat islets
D. Janjic and C. B. Wollheim
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.
