Abstract
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 × 10-5M and 2.3 × 10-4M) 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.
Key words
Insulin Release - Serotonin - Serotonin Antagonists - β Cell Membrane - Hypersomatotropism
- MtT-W15 Tumor
1 Presented in part to the 59th Annual Meeting of the Federation of American Societies
for Experimental Biology, April 13-19, 1975, Atlantic City, New Jersey.
2 Supported by Grant MA-2086 from the Medical Research Council of Canada.
