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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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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. |
format | Online Article Text |
id | pubmed-3642024 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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