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

摘要

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 G(i) protein.