Calcium antagonists and islet function. IX. Is extracellular calcium required for insulin release?

The physiological relevance of extracellular Ca2+ and Mg2+ to the process of glucose-induced insulin release is examined in both the isolated perfused rat pancreas and rat isolated pancreatic islets. When no Ca2+ is added to the perfusion or incubation media, both the initial and late phases of insulin release are severely impaired. The effect of Ca2+ deprivation is an immediate and immediately reversible phenomenon, although the length of the period of Ca2+ deprivation prior to stimulation with glucose modulates the severity of the impairment in the secretory response. When Mg2+ is omitted from the media, the response to glucose occurs precociously and at a higher than normal rate, such a facilitation being a rapid phenomenon. When both Ca2+ and Mg2+ are removed from the extracellular milieu, the secretory response may occur in a normal fashion, except for an earlier onset. The rate of secretion is only reduced after or during a prolonged exposure of the endocrine pancreas to media deprived of both Ca2+ and Mg2+. The release of insulin evoked by glucose in the absence of Ca2+ and Mg2+ is enhanced by theophylline, partially inhibited by verapamil, and abolished by the Ca2+-chelator EGTA. It is concluded that Mg2+, in physiological concentration, exerts an inhibitory effect upon the process of glucose-induced insulin release. However, even in the absence of extracellular Mg2+, the secretory process remains apparently dependent on the availability of minute amounts of extracellular Ca2+.