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The protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats

BACKGROUND: Insulin resistance is strongly associated with the development of type 2 diabetes and cardiovascular disease. However, the underlying mechanisms linking insulin resistance and the development of atherosclerosis have not been fully elucidated. Moreover, the protective effect of antihyperg...

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Autores principales: Lu, Jianxin, Ji, Jingzhang, Meng, Howard, Wang, David, Jiang, Bo, Liu, Lixin, Randell, Edward, Adeli, Khosrow, Meng, Qing H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3642024/
https://www.ncbi.nlm.nih.gov/pubmed/23561047
http://dx.doi.org/10.1186/1475-2840-12-58
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author Lu, Jianxin
Ji, Jingzhang
Meng, Howard
Wang, David
Jiang, Bo
Liu, Lixin
Randell, Edward
Adeli, Khosrow
Meng, Qing H
author_facet Lu, Jianxin
Ji, Jingzhang
Meng, Howard
Wang, David
Jiang, Bo
Liu, Lixin
Randell, Edward
Adeli, Khosrow
Meng, Qing H
author_sort Lu, Jianxin
collection PubMed
description BACKGROUND: Insulin resistance is strongly associated with the development of type 2 diabetes and cardiovascular disease. However, the underlying mechanisms linking insulin resistance and the development of atherosclerosis have not been fully elucidated. Moreover, the protective effect of antihyperglycemic agent, metformin, is not fully understood. This study investigated the protective effects and underlying mechanisms of metformin in balloon-injury induced stenosis in insulin resistant rats. METHODS: After 4 weeks high fructose diet, rats received balloon catheter injury on carotid arteries and were sacrificed at 1 and 4 weeks post injury. Biochemical, histological, and molecular changes were investigated. RESULTS: Plasma levels of glucose, insulin, total cholesterol, triglyceride, free fatty acids, and methylglyoxal were highly increased in fructose-induced insulin resistant rats and treatment with metformin significantly improved this metabolic profile. The neointimal formation of the carotid arteries was enhanced, and treatment with metformin markedly attenuated neointimal hyperplasia. A significant reduction in BrdU-positive cells in the neointima was observed in the metformin-treated group (P < 0.01). Insulin signaling pathways were inhibited in insulin resistant rats while treatment with metformin enhanced the expression of insulin signaling pathways. Increased expression of JNK and NFKB was suppressed following metformin treatment. Vasoreactivity was impaired while treatment with metformin attenuated phenylephrine-induced vasoconstriction and enhanced methacholine-induced vasorelaxation of the balloon injured carotid arteries in insulin resistant rats. CONCLUSION: The balloon-injury induced neointimal formation of the carotid arteries is enhanced by insulin resistance. Treatment with metformin significantly attenuates neointimal hyperplasia through inhibition of smooth muscle cell proliferation, migration, and inflammation as well as by improvement of the insulin signaling pathway.
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spelling pubmed-36420242013-05-03 The protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats Lu, Jianxin Ji, Jingzhang Meng, Howard Wang, David Jiang, Bo Liu, Lixin Randell, Edward Adeli, Khosrow Meng, Qing H Cardiovasc Diabetol Original Investigation BACKGROUND: Insulin resistance is strongly associated with the development of type 2 diabetes and cardiovascular disease. However, the underlying mechanisms linking insulin resistance and the development of atherosclerosis have not been fully elucidated. Moreover, the protective effect of antihyperglycemic agent, metformin, is not fully understood. This study investigated the protective effects and underlying mechanisms of metformin in balloon-injury induced stenosis in insulin resistant rats. METHODS: After 4 weeks high fructose diet, rats received balloon catheter injury on carotid arteries and were sacrificed at 1 and 4 weeks post injury. Biochemical, histological, and molecular changes were investigated. RESULTS: Plasma levels of glucose, insulin, total cholesterol, triglyceride, free fatty acids, and methylglyoxal were highly increased in fructose-induced insulin resistant rats and treatment with metformin significantly improved this metabolic profile. The neointimal formation of the carotid arteries was enhanced, and treatment with metformin markedly attenuated neointimal hyperplasia. A significant reduction in BrdU-positive cells in the neointima was observed in the metformin-treated group (P < 0.01). Insulin signaling pathways were inhibited in insulin resistant rats while treatment with metformin enhanced the expression of insulin signaling pathways. Increased expression of JNK and NFKB was suppressed following metformin treatment. Vasoreactivity was impaired while treatment with metformin attenuated phenylephrine-induced vasoconstriction and enhanced methacholine-induced vasorelaxation of the balloon injured carotid arteries in insulin resistant rats. CONCLUSION: The balloon-injury induced neointimal formation of the carotid arteries is enhanced by insulin resistance. Treatment with metformin significantly attenuates neointimal hyperplasia through inhibition of smooth muscle cell proliferation, migration, and inflammation as well as by improvement of the insulin signaling pathway. BioMed Central 2013-04-05 /pmc/articles/PMC3642024/ /pubmed/23561047 http://dx.doi.org/10.1186/1475-2840-12-58 Text en Copyright © 2013 Lu et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Investigation
Lu, Jianxin
Ji, Jingzhang
Meng, Howard
Wang, David
Jiang, Bo
Liu, Lixin
Randell, Edward
Adeli, Khosrow
Meng, Qing H
The protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats
title The protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats
title_full The protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats
title_fullStr The protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats
title_full_unstemmed The protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats
title_short The protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats
title_sort protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3642024/
https://www.ncbi.nlm.nih.gov/pubmed/23561047
http://dx.doi.org/10.1186/1475-2840-12-58
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