Studies on the role of calcium in insulin secretion from a transplantable hamster insulinoma were performed utilizing dispersed cell suspensions. Insulin release was positively correlated with the extracellular calcium concentration. Potassium (40 mM) and ouabain (10-3M) induced an increased calcium uptake by cells and a concomitant increase in insulin release. Verapamil (10-5M) reduced calcium uptake and insulin release in a parallel manner indicating that the calcium uptake was related to the insulin release. Glucagon, which stimulates insulin release by an adenosine 3′,5′-monophosphate (cAMP)-mediated mechanism, had no effect on calcium uptake and insulin release induced by glucagon was unaffected by verapamil. Therefore, cyclic AMP mediated insulin release does not appear to be the consequence of stimulation of calcium uptake. Glucose, which was transported and phosphorylated by insulinoma cells, did not induce calcium 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 calcium influx. Somatostatin inhibited insulin release irrespective of the stimuli and did so without affecting calcium uptake indicating that somatostatin action is not analogous to other known inhibitors of calcium 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 calcium and cAMP in insulin secretion.
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