Physiological concentrations of oxytocin powerfully stimulate insulin secretionin vitro.

The effect of natural oxytocin on insulin secretion was investigated by using isolated, perfused rat pancreases. Oxytocin produced a dose-dependent stimulation of insulin secretion starting with a concentration as low as 2.3PM: and with a maximal effect obtained at 66PM: . Specific oxytocin antagonist, desGly-NH(2) (9), d(CH(2))(5) [Tyr (Me)(2), Thr(4)] OVT, reduced by 70% the stimulatory effect of 66PM: natural oxytocin. A specific oxytocin receptor agonist OH(Thr(4), Gly(7))OT showed an insulinotropic action similar to equivalent amounts of oxytocin. Replacement or modifications of Q(4), L(8) or the NH(2) terminal group in the oxytocin molecule reduced or abolished the biological activity. This study demonstrated that: (1) in normal rat pancreas, oxytocin stimulates insulin secretion at concentrations similar to those present in the plasma; (2) oxytocin exerts this secretagogue action in presence of basal physiological glucose levels (5 mM); (3) oxytocin stimulates insulin secretion by interacting with its own receptor. A potential role for oxytocin as an insulin-releasing hormone is thus conceivable.