Postconditioning with curaglutide, a novel GLP-1 analog, protects against heart ischemia-reperfusion injury in an isolated rat heart
| Autor: | Klaus D. Döhler, Henrik. K. Salling, Thomas Engstrøm, Marek Treiman |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Cardiac function curve Cardiotonic Agents Physiology Clinical Biochemistry Diastole Ischemia Myocardial Reperfusion Injury In Vitro Techniques Pharmacology Biochemistry Glucagon-Like Peptide-1 Receptor Rats Sprague-Dawley Cellular and Molecular Neuroscience Endocrinology Glucagon-Like Peptide 1 Receptors Glucagon Ventricular Pressure medicine Animals Myocardial infarction business.industry medicine.disease Coronary Vessels Peptide Fragments Rats medicine.anatomical_structure Ventricle Area Under Curve Anesthesia Anorectic business Exenatide Reperfusion injury medicine.drug |
| Zdroj: | Regulatory Peptides. 178:51-55 |
| ISSN: | 0167-0115 |
| Popis: | GLP-1(7-36)amide (GLP-1) is an intestinal hormone with effects on glucose metabolism and feeding behavior, including insulinotropic, insulinomimetic, glucagonostatic and anorectic actions. In experimental settings, GLP-1 has also been shown to diminish infarct size following heart ischemia-reperfusion. GLP-1 analogs with extended half-lives are continuously being developed against type 2 diabetes mellitus. Of these, only exendin-4 (exenatide, registered as Byetta) has been shown to mimic the infarct size-limiting effect of GLP-1 in a clinically relevant application as a postconditioning agent. The aim of this work was to test, in a postconditioning mode, a novel, proteolysis-resistant GLP-1 analog N-Ac-GLP-1(7-34)amide, herein termed curaglutide, for its cardioprotective ability.Global ischemia (35 min)-reperfusion (120 min) was applied in isolated, retrogradely perfused rat hearts. Peptides were present for 15 min at the onset of reperfusion. Cardiac function parameters (beats per minute, left ventricle developed and diastolic pressures, rate-pressure product) were measured. Infarct size was determined by 2,3,5-tripehyltetrazolium chloride staining and planimetry.Curaglutide did not affect any of the functional heart parameters when administered without preceding ischemia. Curaglutide 0.3 nM diminished significantly the postischemic hypercontracture, with no significant effect on the left ventricle developed pressure or rate-pressure product. Infarct size was reduced by curaglutide postconditioning from 24.8% (SEM 2.8, N=14) to 11.4% (SEM 3.2, N=8; P0.05). These effects of curaglutide on postischemic hypercontracture and infarct size were similar in magnitude to corresponding effects of GLP-1 receptor agonist exendin-4. The cardioprotective effects of both agents were abolished in the presence of a GLP-1 receptor antagonist exendin(9-39).Curaglutide is a new, proteolysis-resistant GLP-1 analog with a beneficial effect on reperfusion-injury in an isolated rat heart. Curaglutide was here shown to act through GLP-1 receptors. Based on the present results, more extensive experimental studies in vivo, comparing dose-response characteristics and efficacy of curaglutide and exendin-4 appear warranted. |
| Databáze: | OpenAIRE |
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