title: 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.
  
  
  CONCLUSIONS
  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.affiliation: 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
authors.forename: Ramona A
authors.initials: RA
authors.lastname: Silvestre
authors.forename: Eva M
authors.initials: EM
authors.lastname: Egido
authors.forename: Raquel
authors.initials: R
authors.lastname: Hernández
authors.forename: José
authors.initials: J
authors.lastname: Marco
mesh_terms: D000818:Animals; D000077270:Exenatide; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D010477:Perfusion; D037342:Pertussis Toxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014579:Urotensins / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology
chemical_list: D007328:Insulin; D010455:Peptides; D014579:Urotensins; D014688:Venoms; C029677:urotensin II; D000077270:Exenatide; D037342:Pertussis Toxin; D005947:Glucose