Responses of Patients with Insulinomas to Stimulators and Inhibitors of Insulin Release That Have Been Linked with Cyclic Adenosine Monophosphate

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Abstract
The study comprises nine consecutive patients who had pancreatic beta-cell tumors and spontaneous hypoglycemia, seven of whom had verified, benign insulinomas and one a malignant insulinoma with metastases to the liver. The ninth patient, who refused surgery, was followed for three years without displaying any signs of malignancy. Among the patients with benign insulinomas, three showed exaggerated, two normal, and two unusual insulin responses to glucose. One such patient as well as the one with a malignant tumor did not respond to glucose. In general, the insulin responses to glucagon were similar to those to glucose. Somatostatin reduced basal insulin levels as well as the responses to glucose and glucagon only in subjects with normal or exaggerated responses to these agents. Einephrine behaved like somatostatin when insulin release was stimulated by glucose, but it was a weak inhibitor of the glucagon-stimulated response. The subject with the malignant insulinoma did not respond to either glucose or somatostatin. The remission of the disease, which followed streptozotocin treatment, was accompanied by restoration of the normal responsiveness to the above agents. Glucagon stimulates insulin release by increasing the intracellular level of cyclic adenosine monophosphate (AMP). The effects of glucose, somatostatin, and epinephrine are supposed to be mediated, at least partially, by way of the adenylcyclase-cyclic AMP system. Therefore, the present data suggest that the variability of the beta-cell responsiveness to glucose and glucagon in patients with insulinoma reflects the responsiveness of the adenylcyclase-cyclic AMP system of the beta-cell tumor, which may be exaggerated, normal, or absent.