EFFECTS OF VASOPRESSIN ON INSULIN-SECRETION AND INOSITOL PHOSPHATE PRODUCTION IN A HAMSTER BETA-CELL LINE (HIT)

The recent isolation of vasopressin (VP) fromthe rat and human pancreas led us to investigate the effects of VP on insulin secretion. In the SV 40-transformed hamster betacell line (HIT), 0.1-1.0 nM VP caused rapid stimulation of insulin secretion. Slight but significant inhibition of insulin secretion was observed in the presence of 10 pM VP. These effects of VP on insulin secretion were paralleled by dosedependentchanges in inositol phosphate (IP) production, indicatingmediation by V1 -type VP receptors. VP stimulated IP3 production at 30 sec and production of IP1 by 60 sec. VP (0.1 nM to 1/µM) failed to stimulate the release or cellular content of cAMP, whereas forskolin was an effective stimulus. Forskolinand VP together caused at least additive stimulation of insulin secretion. Taken together, these observations indicate that VP is not acting via V2 -mediated pathways. However, VP-induced stimulation of insulin and IP production were only slightlyinhibited by a V1a pressor antagonist in 100- or 1, 000-fold excess, indicating that VP effects are not mediated by V1a receptors.The V1 receptor involved may represent a V1b or a novel type of VP receptor. These observations suggest a potential physiologicalrole of VP in regulating insulin secretion. © 1990 by The Endocrine Society.