Abstract
BackgroundThe aim of this study was to investigate whether obestatin (OB), a peptide mediator encoded by the ghrelin gene exerting a protective effect in ischemic reperfused heart, is able to reduce cardiac dysfunctions in adult diabetic rats.MethodsDiabetes was induced by STZ injection (50 mg/kg) in Wistar rats (DM). OB was administered (25 μg/kg) twice a day for 6 weeks. Non-diabetic (ND) rats and DM rats were distributed into four groups: untreated ND, OB-treated ND, untreated DM, OB-treated DM. Cardiac contractility and ß-adrenergic response were studied on isolated papillary muscles. Phosphorylation of AMPK, Akt, ERK1/2 and GSK3ß as well ß-1 adrenoreceptors levels were detected by western blot, while α-MHC was measured by RT-PCR.ResultsOB preserved papillary muscle contractility (85 vs 27% of ND), ß-adrenergic response (103 vs 65% of ND), as well ß1-adrenoreceptors and α-MHC levels in diabetic myocardial tissue. Moreover, OB up-regulated the survival kinases Akt and ERK1/2, and enhanced AMPK and GSK3ß phosphorylation. OB corrected oxidative unbalance, reduced pro-inflammatory cytokine TNF-α plasma levels, NFkB translocation and pro-fibrogenic factors expression in diabetic myocardium.ConclusionsOB displays a significant beneficial effect against the alterations of contractility and ß-adrenergic response in the heart of STZ-treated diabetic rats, which was mainly associated with the ability of OB to up-regulate the transcription of ß1-adrenergic receptors and α-MHC; this protective effect was accompanied by the ability to restore oxidative balance and to promote phosphorylation/modulation of AMPK and pro-survival kinases such as Akt, ERK1/2 and GSK3ß.
Highlights
Obestatin (OB) is a newly discovered peptide encoded by the ghrelin gene together with acylated (AG) and unacylated ghrelin (UAG), produced in the oxyntic mucosa of the stomach [1,2,3]
OB improves myocardial function and reduces cell death and apoptosis of cardiomyocytes after ischemia/reperfusion (I/R) in isolated rat heart [18]. These effects are probably mediated by OB receptors present on cardiac cells and by activation of signaling pathways included in the reperfusion injury salvage kinases (RISK), such as phosphoinositide 3-kinase (PI3K), protein kinase C (PKC) and extracellular signal regulated kinases (ERK) 1/2 [18]
The main results obtained in this study suggest that OB displayed a beneficial effect against the reduction of contractility and β-adrenergic response, as well of α-myosin heavy chain (MHC) and β-1 adrenoreceptors expression in the heart of STZ-treated diabetic rats, and that the protective effect is probably related to the ability of OB to restore oxidative balance and to promote phosphorylation/modulation of AMPK and pro-survival kinases such as Akt, ERK1/2 and glycogen synthase kinase (GSK) 3β
Summary
Obestatin (OB) is a newly discovered peptide encoded by the ghrelin gene together with acylated (AG) and unacylated ghrelin (UAG), produced in the oxyntic mucosa of the stomach [1,2,3]. OB improves myocardial function and reduces cell death and apoptosis of cardiomyocytes after ischemia/reperfusion (I/R) in isolated rat heart [18] These effects are probably mediated by OB receptors present on cardiac cells and by activation of signaling pathways included in the reperfusion injury salvage kinases (RISK), such as phosphoinositide 3-kinase (PI3K), protein kinase C (PKC) and extracellular signal regulated kinases (ERK) 1/2 [18]. The protective effects exerted by OB against myocardial dysfunctions in ischemic-reperfused heart led us to investigate whether OB may rescue myocardial contractility and beta adrenergic response in the heart of STZ treated diabetic rats. The aim of this study was to investigate whether obestatin (OB), a peptide mediator encoded by the ghrelin gene exerting a protective effect in ischemic reperfused heart, is able to reduce cardiac dysfunctions in adult diabetic rats
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
