The Role of Calcium in Insulin Release from Hamster Insulinoma Cells1

Abstract

Studies on the role of Ca in insulin secretion from a transplantable hamster insulinoma were performed utilizing dispersed cell suspensions. Insulin release was positively correlated with the extracellular Ca concentration. K (40 mM) and ouabain (10-3 M) induced an increased Ca uptake by cells and a concomitant increase in insulin release. Verapamil (10-5 M) reduced Ca uptake and insulin release in a parallel manner indicating that Ca uptake was related to insulin release. Glucagon, which stimulates insulin release by a c[cyclic]AMP-mediated mechanism, had no effect on Ca uptake, and insulin release induced by glucagon was unaffected by verapamil. cAMP mediated insulin release does not appear to be the consequence of stimulation of Ca uptake. Glucose, which was transported and phosphorylated by insulinoma cells, did not induce Ca uptake or insulin release. In normal islets glucose did both. The results suggest that the defect in glucose action in these cells is the result of a failure of glucose to induce a Ca influx. Somatostatin inhibited insulin release irrespective of the stimuli and did so without affecting Ca uptake indicating that somatostatin action is not analogous to other known inhibitors of Ca uptake. The Syrian hamster transplantable insulinoma represents a model of insulin secretion unresponsive to glucose, but analogous to normal islets in terms of the role of Ca and cAMP in insulin secretion.