| Effect of the urotensin-II receptor antagonist palosuran on secretion of and sensitivity to insulin in patients with Type 2 diabetes mellitus. | |
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MedLine Citation:
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PMID: 19843053 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: To investigate the effects of palosuran, a nonpeptidic, potent and selective antagonist of the urotensin-II receptor, on insulin and glucose regulation in 20 diet-treated patients with Type 2 diabetes mellitus in a double-blind, placebo-controlled, randomized, crossover, proof-of-concept study. METHODS: After 4 weeks' oral treatment with 125 mg palosuran or placebo b.i.d.,effects on insulin secretion and sensitivity and blood glucose levels were assessed by means of a hyperglycaemic glucose clamp, meal tolerance test, homeostasis model assessment-insulin resistance score, and daily self-monitoring of blood glucose. Plasma concentrations of palosuran were determined for 12 h on the last day of intake. RESULTS: Palosuran did not affect second-phase insulin response (primary end-point) during the hyperglycaemic glucose clamp in comparison with placebo [paired difference of -1.8 microU ml(-1), 95% confidence interval (CI) -7.8, 4.2]. Likewise, no effects of palosuran were detected on the first-phase insulin response, or on insulin secretion and blood glucose levels during the meal tolerance test or on homeostasis model assessment-insulin resistance score. No clinically significant effects on daily blood glucose profiles were observed during the study. Geometric mean C(max) and AUC(tau) (95% CI) and median t(max) (range) in this patient population were 180 ng ml(-1) (125, 260), 581 ng.h ml(-1) (422, 800) and 3.0 h (0.67, 4.3), respectively. CONCLUSIONS: The results of this study indicate that antagonism of the urotensin-II system does not influence insulin secretion or sensitivity or daily blood glucose levels in diet-treated patients with Type 2 diabetes. |
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Authors:
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Patricia N Sidharta; Klaus Rave; Lutz Heinemann; Eleonora Chiossi; Stephan Krähenbühl; Jasper Dingemanse |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial |
Journal Detail:
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Title: British journal of clinical pharmacology Volume: 68 ISSN: 1365-2125 ISO Abbreviation: Br J Clin Pharmacol Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-21 Completed Date: 2010-07-30 Revised Date: 2010-10-04 |
Medline Journal Info:
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Nlm Unique ID: 7503323 Medline TA: Br J Clin Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 502-10 Citation Subset: IM |
Affiliation:
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Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, CH-4123 Allschwil, Switzerland. patricia.sidharta@actelion.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Blood Glucose / drug effects*, metabolism Diabetes Mellitus, Type 2 / blood*, drug therapy Double-Blind Method Female Glucose Clamp Technique Glucose Tolerance Test Humans Insulin / blood, secretion* Male Middle Aged Quinolines / blood*, therapeutic use Receptors, G-Protein-Coupled / blood* Treatment Outcome Urea / analogs & derivatives*, blood, therapeutic use Urotensins / blood* |
| Chemical | |
Reg. No./Substance:
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0/1-(2-(4-benzyl-4-hydroxypiperidin-1-yl)ethyl)-3-(2-methylquinolin-4-yl)urea; 0/Blood Glucose; 0/Quinolines; 0/Receptors, G-Protein-Coupled; 0/UTS2R protein, human; 0/Urotensins; 11061-68-0/Insulin; 57-13-6/Urea |
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