Ramona A Silvestre1, Eva M Egido, Raquel Hernández, José Marco. 1. Hospital Universitario Puerta de Hierro and Department of Physiology, Medical School, Universidad Autónoma de Madrid, San Martín de Porres 4, 28035 Madrid, Spain. rsilvestre.hpth@salud.madrid.org
Abstract
UNLABELLED: 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.
UNLABELLED: 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.
Authors: María E Sáez; Tarik Smani; Reposo Ramírez-Lorca; Ignacio Díaz; Manuel Serrano-Ríos; Agustín Ruiz; Antonio Ordoñez Journal: PLoS One Date: 2011-04-29 Impact factor: 3.240