Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas

• Published in: European journal of endocrinology Vol. 151; no. 6; pp. 803 - 809
• Main Authors: SILVESTRE, Ramona A, EGIDO, Eva M, HERNANDEZ, Raquel, LEPRINCE, Jarome, CHATENET, David, TOLLEMER, Hélène, CHARTREL, Nicolas, VAUDRY, Hubert, MARCO, José
• Format: Journal Article
• Language: English
• Published: Colchester Portland Press 01.12.2004; Oxford Univ. Press
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Animals; Biological and medical sciences; Blood Glucose; Blood Glucose - metabolism; Calcium Channel Agonists; Calcium Channel Agonists - pharmacology; Carbachol; Carbachol - pharmacology; Cell Behavior; Cellular Biology; Chemical Sciences; Chromatography, High Pressure Liquid; Depression, Chemical; Endocrinopathies; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Insulin; Insulin - metabolism; Life Sciences; Male; Medical sciences; Medicinal Chemistry; Neurobiology; Neurons and Cognition; Pancreas; Pancreas - drug effects; Pancreas - metabolism; Pancreatic Extracts; Pancreatic Extracts - chemistry; Parasympathomimetics; Parasympathomimetics - pharmacology; Pharmaceutical sciences; Pharmacology; Radioimmunoassay; Rats; Rats, Wistar; Structure-Activity Relationship; Urotensins; Urotensins - chemistry; Urotensins - metabolism; Urotensins - pharmacology; Vertebrates: endocrinology; Pancreatic hormone; Rat; Rodentia; Extract; Insulin; Hypothalamic hormone; Vertebrata; Mammalia; Animal; Inhibitor; Urotensin II; Pancreas; Endocrinology; Release
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/eje.0.1510803

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. 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. 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. 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.