PHYSIOLOGICAL CONCENTRATIONS OF OXYTOCIN POWERFULLY STIMULATE INSULIN-SECRETION IN-VITRO

The effect of natural oxytocin on insulin secretion was investigated b y using isolated, perfused rat pancreases. Oxytocin produced a dose-de pendent stimulation of insulin secretion starting with a concentration as low as 2.3 pM and with a maximal effect obtained at 66 pM. Specifi c oxytocin antagonist, desGly-NH2 (9), d(CH2)(5) [Tyr (Me)(2), Thr(4)] OVT, reduced by 70% the stimulatory effect of 66 pM natural oxytocin. A specific oxytocin receptor agonist OH(Thr(4), Gly(7))OT showed an i nsulinotropic action similar to equivalent amounts of oxytocin. Replac ement or modifications of Q(4), L(8) or the NH2 terminal group in the oxytocin molecule reduced or abolished the biological activity. This s tudy demonstrated that: (1) in normal rat pancreas, oxytocin stimulate s insulin secretion at concentrations similar to those present in the plasma; (2) oxytocin exerts this secretagogue action in presence of ba sal physiological glucose levels (5 mM); (3) oxytocin stimulates insul in secretion by interacting with its own receptor. A potential role fo r oxytocin as an insulin-releasing hormone is thus conceivable.