Endogenous ornithine decarboxylase/polyamine system mediated the antagonist role of insulin/PEG-CMCS preconditioning against heart ischemia/reperfusion injury in diabetes mellitus
Authors Tong F, Liu S, Yan B, Li X, Ruan S, Yang S
Received 26 December 2017
Accepted for publication 6 March 2018
Published 23 April 2018 Volume 2018:13 Pages 2507—2520
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Linlin Sun
Fei Tong,1,2 Suhuan Liu,1 Bing Yan,1 Xuejun Li,1 Shiwei Ruan,3 Shuyu Yang1
1Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China; 2Department of Pathology and Pathophysiology, Provincial Key Discipline of Pharmacology, Jiaxing University Medical College, Jiaxing, China; 3Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
Introduction: Insulin has shown antioxidation and cytoprotective effects to decrease heart ischemia/reperfusion injury (HI/RI) in diabetes mellitus (DM), but the role of insulin/poly(ethylene glycol)-carboxymethyl chitosan (PEG-CMCS) on HI/RI in DM is not known. This research explored whether insulin/PEG-CMCS revealed a protective effect on HI/RI in DM through ornithine decarboxylase (ODC)/polyamine systems.
Materials and methods: Diabetes was induced via streptozotocin (STZ) in Sprague Dawley (SD) rats, which suffered from HI via blocking the left circumflex artery for 45 minutes, followed by 2 hours of reperfusion. α-Difluoromethylornithine-ethylglyoxal bis (guanylhydrazone) (DFMO-EGBG) and insulin/PEG-CMCS were administered to diabetic rats to explore their roles on severity of HI/RI.
Results: Insulin could be fleetly and efficiently loaded via the nanocarrier PEG-CMCS at pH =6, showing efficient loading and stable release. In addition, insulin/PEG-CMCS showed significant hypoglycemic activity in diabetic rats. On the other hand, ischemia/reperfusion obviously augmented the contents of creatine kinase (CK), lactic dehydrogenase (LDH), putrescine (Pu), myocardial infarct size, and NF-κB and spermidine/spermine N′-acetyltransferase (SSAT) expressions and decreased the levels of spermine (Sp), polyamine pools (PAs), heart rate (HR), coronary blood flow (CF), left ventricular developed pressure (LVDP), and ODC expression, compared with Sham. Administration of insulin and insulin/PEG-CMCS both reduced the contents of CK, LDH, Pu, myocardial infarct size, and NF-κB and SSAT expressions and increased the levels of Sp, PAs, HR, CF, LVDP, and ODC expression, while insulin/PEG-CMCS significantly indicated the protective results, and DFMO-EGBG showed the opposite effects.
Conclusion: The research showed that insulin/PEG-CMCS could play a protective effect on HR/RI in diabetic rats via its antioxidative, antiapoptotic, and anti-inflammatory roles and modulating ODC/polyamine systems.
Keywords: heart ischemia/reperfusion injury, PEG-CMCS, diabetes mellitus, heart function, ODC/polyamine, NF-κB, apoptosis
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]