Effects of cyproheptadine on insulin secretion by isolated perifused rat islets

The effects of cyproheptadine on basal and glucose-induced insulin release by isolated rat islets was studied by use of a perifusion system. A forty-five minute preincubation of islets with a medium containing both 34.3 mug./ml. (10(-4) M) cyproheptadine and 1.0 mg./ml. glucose completely abolished the biphasic pattern of increased insulin secretion normally obtained after islets are stimulated with a medium containing 3.0 mg./ml. glucose. In another series of experiments, similar results were obtained when the cyproheptadine and 3.0 mg./ml. glucose were presented together. Here, however, the inhibition of the first phase of insulin secretion did not achieve statistical significance and some recovery of the islets' secretory capacity was observed late during the second phase. In studies designed to investigate the influence of cyproheptadine on basal insulin secretion, no obvious effect was observed. These results are discussed in relation to the species-specific alterations in pancreatic beta-cell morphology that have been reported in rats after the oral administration of cyproheptadine.