Abstract
ABSTRACTPurposeThe present study explored the influence of liraglutide on remote preconditioning-mediated cardioprotection in diabetes mellitus along with the role of nuclear factor erythroid 2-related factor 2 (Nrf2), hypoxia inducible factor (HIF-1α) and hydrogen sulfide (H2S).MethodsStreptozotocin was given to rats to induce diabetes mellitus and rats were kept for eight weeks. Four cycles of ischemia and reperfusion were given to hind limb to induce remote preconditioning. After 24 h, hearts were isolated and subjected to 30 min of ischemia and 120 min of reperfusion on Langendorff system. Liraglutide was administered along with remote preconditioning. Cardiac injury was assessed by measuring the release of creatine kinase (CK-MB), cardiac troponin (cTnT) and development of left ventricular developed pressure. After ischemia-reperfusion, hearts were homogenized to measure the nuclear cytoplasmic ratio of Nrf2, H2S and HIF-1α levels.ResultsIn diabetic rats, there was more pronounced injury and the cardioprotective effects of remote preconditioning were not observed. Administration of liraglutide restored the cardioprotective effects of remote preconditioning in a dose-dependent manner. Moreover, liraglutide increased the Nrf2, H2S and HIF-1α levels in remote preconditioning-subjected diabetic rats.ConclusionsLiraglutide restores the lost cardioprotective effects of remote preconditioning in diabetes by increasing the expression of Nrf2, H2S and HIF-1α.
Highlights
Diabetes mellitus is a chronic metabolic disorder, which is characterized by disturbance in glucose metabolism
Liraglutide is glucagon-like peptide 1 agonist (GLP-1 agonist) and it has been used to manage diabetes mellitus type 27
It is shown that liraglutide increases the expression of Nrf[2], a transcriptional factor involved in increasing antioxidant enzymes, in producing beneficial effects[19,20]
Summary
Diabetes mellitus is a chronic metabolic disorder, which is characterized by disturbance in glucose metabolism. Remote preconditioning a therapeutic strategy in which short episodes of ischemia and reperfusion to an organ other than heart (nontarget or remote organ) confers protection to heart from sustained ischemia-reperfusion injury[3]. This therapeutic strategy has been used in preclinical as well in clinical setup to confer protection to heart against ischemiareperfusion injury[4,5]. Liraglutide is glucagon-like peptide 1 agonist (GLP-1 agonist) and it has been used to manage diabetes mellitus type 27. The role of Nrf[2] ratio[13,14], HIF-1α15,16 and H2S17 has been very well documented in remote preconditioning-induced cardioprotection. It is shown that liraglutide increases the expression of Nrf[2], a transcriptional factor involved in increasing antioxidant enzymes, in producing beneficial effects[19,20]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
