Comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance

Abstract Impaired glucose tolerance (IGT) increases cardiovascular risk and can enlarge myocardial infarction (MI) incidence and severity. There is lack of information about cardioprotective potential of glucose-lowering drugs in IGT. We aimed to evaluate the sustainability of myocardium to ischemia...

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Autores principales:	Anna Simanenkova, Sarkis Minasian, Tatiana Karonova, Timur Vlasov, Natalya Timkina, Oksana Shpilevaya, Aleksandra Khalzova, Anzhelika Shimshilashvili, Valeria Timofeeva, Daniil Samsonov, Yury Borshchev, Michael Galagudza
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7916bad8a0fc4ce5bf35c4f5a2338ae7
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spelling	oai:doaj.org-article:7916bad8a0fc4ce5bf35c4f5a2338ae72021-12-02T14:02:53ZComparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance10.1038/s41598-021-86132-22045-2322https://doaj.org/article/7916bad8a0fc4ce5bf35c4f5a2338ae72021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86132-2https://doaj.org/toc/2045-2322Abstract Impaired glucose tolerance (IGT) increases cardiovascular risk and can enlarge myocardial infarction (MI) incidence and severity. There is lack of information about cardioprotective potential of glucose-lowering drugs in IGT. We aimed to evaluate the sustainability of myocardium to ischemia–reperfusion injury in diabetic and IGT rats and to study cardioprotective action of metformin and liraglutide. Type 2 diabetes mellitus (DM) and IGT were modelled in Wistar rats by high-fat diet and streptozotocin + nicotinamide. 4 weeks after rats were divided into 4 groups: DM (without treatment) (n = 4), IGT (without treatment) (n = 4), IGT + MET (metformin 200 mg/kg per os once daily 8 weeks) (n = 4), IGT + LIRA (liraglutide 0.06 mg/kg s.c. once daily for 8 weeks) (n = 4). Control (n = 6) and high-fat diet (n = 8) groups were made for comparison. After 8 weeks ischemia–reperfusion injury in isolated hearts was performed. Hemodynamic parameters were evaluated and MI size was measured by staining of myocardium slices in triphenyltetrazolium chloride solution. Blood glucose level was measured during the study. Both IGT and DM led to similar worsening of hemodynamic parameters during ischemia–reperfusion period, in comparison with control group. MI size in IGT (56.76 (51.58; 69.07) %) and DM (57.26 (45.51; 70.08) %) groups was significantly larger than that in control group (42.98 (33.26; 61.84) %) and did not differ between each other. MI size in high-fat diet group (56.98 (47.11; 62.83) %) was as large as in IGT and DM groups (p > 0.05). MI size in IGT + MET (42.11 (38.08; 71.96) %) and IGT + LIRA (42.50 (31.37; 60.40) %) was smaller than in both DM and IGT groups (p < 0.05 for multiple comparison). Myocardium damage size did not differ in IGT + MET and IGT + LIRA groups (p > 0.05). Only LIRA, but not MET administration to IGT rats led to ischemic contracture reduction. Glycemic control was similarly satisfactory in IGT, IGT + MET, IGT + LIRA groups. Thus, IGT and DM have similarly pronounced negative influence on hemodynamics and MI size in rat transient global ischemia ex vivo. Obesity development also has negative impact on the MI size. Both MET and LIRA have infarct-limiting effect independent on their influence on glucose level. LIRA, but not MET, diminishes ischemic contracture in IGT rats.Anna SimanenkovaSarkis MinasianTatiana KaronovaTimur VlasovNatalya TimkinaOksana ShpilevayaAleksandra KhalzovaAnzhelika ShimshilashviliValeria TimofeevaDaniil SamsonovYury BorshchevMichael GalagudzaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Simanenkova Sarkis Minasian Tatiana Karonova Timur Vlasov Natalya Timkina Oksana Shpilevaya Aleksandra Khalzova Anzhelika Shimshilashvili Valeria Timofeeva Daniil Samsonov Yury Borshchev Michael Galagudza Comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance
description	Abstract Impaired glucose tolerance (IGT) increases cardiovascular risk and can enlarge myocardial infarction (MI) incidence and severity. There is lack of information about cardioprotective potential of glucose-lowering drugs in IGT. We aimed to evaluate the sustainability of myocardium to ischemia–reperfusion injury in diabetic and IGT rats and to study cardioprotective action of metformin and liraglutide. Type 2 diabetes mellitus (DM) and IGT were modelled in Wistar rats by high-fat diet and streptozotocin + nicotinamide. 4 weeks after rats were divided into 4 groups: DM (without treatment) (n = 4), IGT (without treatment) (n = 4), IGT + MET (metformin 200 mg/kg per os once daily 8 weeks) (n = 4), IGT + LIRA (liraglutide 0.06 mg/kg s.c. once daily for 8 weeks) (n = 4). Control (n = 6) and high-fat diet (n = 8) groups were made for comparison. After 8 weeks ischemia–reperfusion injury in isolated hearts was performed. Hemodynamic parameters were evaluated and MI size was measured by staining of myocardium slices in triphenyltetrazolium chloride solution. Blood glucose level was measured during the study. Both IGT and DM led to similar worsening of hemodynamic parameters during ischemia–reperfusion period, in comparison with control group. MI size in IGT (56.76 (51.58; 69.07) %) and DM (57.26 (45.51; 70.08) %) groups was significantly larger than that in control group (42.98 (33.26; 61.84) %) and did not differ between each other. MI size in high-fat diet group (56.98 (47.11; 62.83) %) was as large as in IGT and DM groups (p > 0.05). MI size in IGT + MET (42.11 (38.08; 71.96) %) and IGT + LIRA (42.50 (31.37; 60.40) %) was smaller than in both DM and IGT groups (p < 0.05 for multiple comparison). Myocardium damage size did not differ in IGT + MET and IGT + LIRA groups (p > 0.05). Only LIRA, but not MET administration to IGT rats led to ischemic contracture reduction. Glycemic control was similarly satisfactory in IGT, IGT + MET, IGT + LIRA groups. Thus, IGT and DM have similarly pronounced negative influence on hemodynamics and MI size in rat transient global ischemia ex vivo. Obesity development also has negative impact on the MI size. Both MET and LIRA have infarct-limiting effect independent on their influence on glucose level. LIRA, but not MET, diminishes ischemic contracture in IGT rats.
format	article
author	Anna Simanenkova Sarkis Minasian Tatiana Karonova Timur Vlasov Natalya Timkina Oksana Shpilevaya Aleksandra Khalzova Anzhelika Shimshilashvili Valeria Timofeeva Daniil Samsonov Yury Borshchev Michael Galagudza
author_facet	Anna Simanenkova Sarkis Minasian Tatiana Karonova Timur Vlasov Natalya Timkina Oksana Shpilevaya Aleksandra Khalzova Anzhelika Shimshilashvili Valeria Timofeeva Daniil Samsonov Yury Borshchev Michael Galagudza
author_sort	Anna Simanenkova
title	Comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance
title_short	Comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance
title_full	Comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance
title_fullStr	Comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance
title_full_unstemmed	Comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance
title_sort	comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7916bad8a0fc4ce5bf35c4f5a2338ae7
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Comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance

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