Mechanism of Epinephrine and Serotonin Inhibition of Insulin Release in the Golden Hamster in Vitro

Similarities and differences in the mechanisms by which epinephrine and serotonin inhibit insulin secretion were studied in an in vitro golden hamster pancreas system. Both amines were shown to inhibit the insulin release stimulated by either high glucose (3 mg./ml.) or dibutyryl cyclic AMP 1 mg./ml. The beta adrenergic blocking agent propranolol had no effect on either basal or high glucose-stimulated insulin release. It also was without effect on the serotonin inhibition of high glucose-stimulated insulin release. Phentolamine, an alpha adrenergic blocking agent, prevented the serotonin inhibition of high glucose or dibutyryl cyclic AMP mediated insulin release. Phentolamine also blocked the action of epinephrine in inhibiting dibutyryl cyclic AMP mediated insulin release. The data indicate that both amines block insulin release by interfering with the action of 3′5′ cyclic AMP in causing insulin release. Phentolamine appears to act at the same locus, i.e., in the action of 3′5′ cyclic AMP. The only difference noted between serotonin and epinephrine action on the pancreatic beta cell was that methysergide maleate, a known serotonin antagonist, was able to block serotonin action but not that of epinephrine.