This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by KIKUCHI, M. Articles by SHARP, G. W. G. Search for Related Content PubMed PubMed Citation Articles by KIKUCHI, M. Articles by SHARP, G. W. G.

Studies on the Dual Effects of Glucose on ⁴⁵Ca⁺⁺ Efflux from Isolated Rat Islets^*

MASATOSHI KIKUCHI, CLAES B. WOLLHEIM, GUY S. CUENDET, ALBERT E. RENOLD and GEOFFREY W. G. SHARP

Institut de Biochimie Clinique, University of Geneva Geneva, Switzerland

Abstract

⁴⁵Ca⁺⁺ efflux studies were performed on rat islets of Langerhans which were loaded to isotopic equilibrium during 48 h in tissue cultures. ⁴⁵Ca⁺⁺ loading was 50% complete at 1 h, 80% at 4 h, and reached, at equilibrium, a content equal to 10–11 pmol/islet.

The islets responded to glucose stimulation with a rapid and markedly biphasic insulin release. Under normal conditions, glucose stimulated ⁴⁵Ca⁺⁺ efflux with an initial surge (simultaneous with the first peak of insulin release), which declined rapidly to 50% of the peak value and then slowly declined for the remainder of the glucose stimulation. Special conditions were required to uncover an early inhibition of ⁴⁵Ca⁺⁺ efflux; these were the lowering of the temperature of the perifusate from 37 C to 30 C or below, or reduction of the medium Ca⁺⁺ concentration to 0.1 mM or less. Under zero calcium conditions the glucose inhibition of ⁴⁵Ca⁺⁺ efflux can be rigorously interpreted as an inhibition of calcium efflux.

The studies at low temperature or low Ca⁺⁺ concentrations revealed two effects of glucose on ⁴⁵Ca⁺⁺ efflux: an initial inhibition followed by a stimulation, the inhibitory effect was obscured by the rapidity of onset of the stimulatory effect under normal conditions. At low temperature it was also possible to inhibit glucose-stimulated insulin release, although the stimulated ⁴⁵Ca⁺⁺ efflux remained unchanged. At 30 C or in experiments with 0.3 mM Ca⁺⁺, glucose-stimulated insulin release preceded the stimulation of ⁴⁵Ca⁺⁺ efflux. It therefore, is, concluded that the stimulated ⁴⁵Ca⁺⁺ efflux is a consequence, rather than a determinant, of stimulussecretion coupling. The stimulated efflux is dependent on the presence of Ca⁺⁺ in the medium and is independent of emiocytosis. This latter finding excludes the secretory granules as a significant source of glucose-stimulated ⁴⁵Ca⁺⁺ extrusion. (Endocrinology 102: 1339, 1978)

Footnotes

^* This work was supported by the Swiss National Science Foundation (Grant 3.1060.73).

To whom requests for reprints should be addressed at: Institut de Biochimie Clinique, Sentier de la Roseraie, 1211 Geneve 4, Switzerland.

Received July 21, 1977.