Silvestre, Ramona A.; Egido, Eva M.; Hernandez, Raquel; Leprince, Jérôme; Chatenet, David 
ORCID: https://orcid.org/0000-0002-7270-4328; Tollemer, Hélène; Chartrel, Nicolas; Vaudry, Hubert et Marcoux, José
(2004).
Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas
European Journal of Endocrinology
, vol. 151
, nº 6.
pp. 803-809.
DOI: 10.1530/eje.0.1510803.
Résumé
OBJECTIVE:
Previous work from our laboratory has demonstrated that frog urotensin-II (UII), at a high concentration, inhibits glucose-induced insulin release in the rat pancreas. We have investigated the effect of rat UII and two structural analogs on insulin secretion and searched for the presence of UII-immunoreactivity in rat pancreatic extracts.
METHODS:
The study was performed in the perfused rat pancreas. UII as well as its analogs were synthesized by solid phase methodology. Pancreatic extracts were analyzed for UII by reversed-phase HPLC combined with a sensitive UII RIA.
RESULTS:
Infusion of synthetic rat UII inhibited glucose-induced insulin release in a dose-dependent manner (IC(50): 0.12 nmol/l). UII (1 nmol/l) also inhibited the insulin responses induced by carbachol, glucagon-like peptide-1, and a calcium channel agonist (BAY K 8644). The inhibitory effect of UII was mimicked by the potent G protein-coupled receptor (GPR14) agonist [3-iodo-Tyr(6)]UII(4-11). In contrast, [Ala(8)]UII(4-11), a UII analog devoid of contractile activity on rat aortic rings, did not affect glucose-induced insulin secretion. Analysis of rat pancreatic extracts revealed the presence of an immunoreactive peptide exhibiting the same retention time as synthetic rat UII.
CONCLUSIONS:
Our results demonstrate that UII is a potent insulinostatic peptide. The observation that UII is actually present in the pancreas suggests that this peptide may play a physiological role in the control of insulin secretion. Concerning the two UII analogs tested, only [3-iodo-Tyr(6)]UII(4-11), reportedly possessing GPR14-mediated contractile activity, mimics the insulinostatic effect of UII. This finding would support the view that UII acts on the pancreatic beta cell through the GPR14 receptor.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 21 nov. 2024 20:00 |
| Dernière modification: | 21 nov. 2024 20:39 |
| URI: | https://espace.inrs.ca/id/eprint/15168 |
Gestion Actions (Identification requise)
 |
Modifier la notice |