Oxytocin-stimulated insulin release in a clonal beta-cell line RINm5F: Involvement of phospholipase C-dependent and -independent pathways

AIM: To study the mechanisms underlying oxytocin (Oxy)-induced insulin release. METHODS: in a clonal pancreatic beta-cell line, RINm5F cells. RESULTS: Oxy increased insulin release and [Ca2+](i) in a concentration-dependent manner. Oxy-induced insulin release was not altered by pretreatment with pertussis toxin (PT). U-73122 (2-8 mu mol . L(-1)), a phospholipase C (PLC) inhibitor, concentration-dependently inhibited Oxy-induced increases in [Ca2+](i) with IC50 value of 2.8 +/- 0.2 mu mol . L(-1), In addition, U-73122 diminished the Oxy-induced increase in intracellular concentration of inositol 1,4,5-trisphosphate (IP3). U-73122 at 8 mu mol . L(-1), totally abolished the Oxy-induced increases in [Ca2+](i) and IP3; however it reduced the Oxy-induced increase in insulin release only by 36% and 63% in the monolayer and suspended cell preparations, respectively. CONCLUSION: Oxy increases insulin release through both PLC and non-PLC mediated signal transduction mechanisms.