Effects of Serotonin and its Antagonists on the First Phase of Insulin Release in Normal and Hypersomatotropic Rats

The in situ perfused rat pancreas of normal and hypersomatotropic rats was used to study the effects of serotonin and its antagonists on the release of insulin in the presence of 4.4 mM and 16.6 mM glucose. In normal rats, serotonin (1.0 × 10 -5 M and 2.3 × 10 -4 M) inhibited significantly the glucosemediated first phase of insulin release but did not affect the basal release of insulin (4.4 mM glucose). The serotonin antagonists methysergide maleate (MSM) (1.0 × 10 -4 M), Squibb (SQ) 10,631 (SQ (1.0 × 10 -4 M) and cyproheptadine (Cy) (2.8 × 10 -9 M) blocked the inhibitory action of serotonin. Only MSM potentiated the glucose-mediated first phase of insulin release in the presence and absence of serotonin. At this dose, MSM and SQ each significantly stimulated insulin release in the presence of non-stimulatory glucose concentration (4.4 mM). In hypersomatotropic rats, serotonin inhibited the first phase of glucose-mediated insulin release, but a 20-times higher concentration than that used in normal rats was necessary to obtain the same degree of inhibition. In contrast the antagonists MSM, SQ and Cy did not block the inhibition induced by serotonin. MSM and SQ, however, significantly stimulated insulin release in the presence of 4.4 mM glucose. The results obtained suggest that: a) exogenous and intracellular serotonin might regulate the release of insulin by acting on the β cell membrane; b) β cells from hypersomatotropic rats have a decreased sensitivity to serotonin, and possibly to serotonin antagonists.