Characterization of the insulinostatic effect of urotensin II: A study in the perfused rat pancreas

Abstract: We have investigated the effect of urotensin II (UII) on insulin secretion at normal and high glucose concentrations as well as induced by secretagogues acting on the B cell via different mechanisms. The study was performed in the perfused rat pancreas. UII, at 1 nM, blocked the insulin response to an increase in perfusate glucose concentration from 5.5 to 9 mM while failed to significantly modify insulin secretion at higher glucose levels (from 9 to 13 mM). The insulinotropic effect of this glucose challenge was reduced by 10 nM UII. UII, at 1 nM, inhibited tolbutamide-induced insulin secretion, whereas, it did not affect KCl-induced insulin release. UII inhibited exendin-4-induced insulin secretion, an effect not observed in pertussis toxin-treated rats. Conclusion: 1) B cells are less sensitive to UII at a high glucose level than at a low glucose. 2) The inhibitory effect of UII on both glucose and tolbutamide-induced insulin release, suggests the implication of ATP-dependent K+ channels. The insulinostatic effect of UII was not observed during KCl stimulation, a condition in which these channels are overridden. 3) The insulinostatic effect of UII can also be mediated by its inhibitory action on the adenylate cyclase/cAMP system via a pertussis toxin-sensitive Gi protein. [Copyright &y& Elsevier]