Endogenous ornithine decarboxylase/polyamine system mediated the antagonist role of insulin/PEG-CMCS preconditioning against heart ischemia/reperfusion injury in diabetes mellitus

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...

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Autores principales:	Tong F, Liu S, Yan B, Li X, Ruan S, Yang S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	PEG-CMCS insulin ODC/polyamine NF-κB apoptosis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2a3273ebb68c498392ddc2355addcf45
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spelling	oai:doaj.org-article:2a3273ebb68c498392ddc2355addcf452021-12-02T07:20:52ZEndogenous ornithine decarboxylase/polyamine system mediated the antagonist role of insulin/PEG-CMCS preconditioning against heart ischemia/reperfusion injury in diabetes mellitus1178-2013https://doaj.org/article/2a3273ebb68c498392ddc2355addcf452018-04-01T00:00:00Zhttps://www.dovepress.com/endogenous-ornithine-decarboxylasepolyamine-system-mediated-the-antago-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Fei 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, apoptosisTong FLiu SYan BLi XRuan SYang SDove Medical PressarticlePEG-CMCSinsulinODC/polyamineNF-κBapoptosisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 2507-2520 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	PEG-CMCS insulin ODC/polyamine NF-κB apoptosis Medicine (General) R5-920
spellingShingle	PEG-CMCS insulin ODC/polyamine NF-κB apoptosis Medicine (General) R5-920 Tong F Liu S Yan B Li X Ruan S Yang S Endogenous ornithine decarboxylase/polyamine system mediated the antagonist role of insulin/PEG-CMCS preconditioning against heart ischemia/reperfusion injury in diabetes mellitus
description	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
format	article
author	Tong F Liu S Yan B Li X Ruan S Yang S
author_facet	Tong F Liu S Yan B Li X Ruan S Yang S
author_sort	Tong F
title	Endogenous ornithine decarboxylase/polyamine system mediated the antagonist role of insulin/PEG-CMCS preconditioning against heart ischemia/reperfusion injury in diabetes mellitus
title_short	Endogenous ornithine decarboxylase/polyamine system mediated the antagonist role of insulin/PEG-CMCS preconditioning against heart ischemia/reperfusion injury in diabetes mellitus
title_full	Endogenous ornithine decarboxylase/polyamine system mediated the antagonist role of insulin/PEG-CMCS preconditioning against heart ischemia/reperfusion injury in diabetes mellitus
title_fullStr	Endogenous ornithine decarboxylase/polyamine system mediated the antagonist role of insulin/PEG-CMCS preconditioning against heart ischemia/reperfusion injury in diabetes mellitus
title_full_unstemmed	Endogenous ornithine decarboxylase/polyamine system mediated the antagonist role of insulin/PEG-CMCS preconditioning against heart ischemia/reperfusion injury in diabetes mellitus
title_sort	endogenous ornithine decarboxylase/polyamine system mediated the antagonist role of insulin/peg-cmcs preconditioning against heart ischemia/reperfusion injury in diabetes mellitus
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/2a3273ebb68c498392ddc2355addcf45
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Endogenous ornithine decarboxylase/polyamine system mediated the antagonist role of insulin/PEG-CMCS preconditioning against heart ischemia/reperfusion injury in diabetes mellitus

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