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Metformin accelerates wound healing in type 2 diabetic db/db mice

Wound healing impairment is increasingly recognized to be a consequence of hyperglycemia-induced dysfunction of endothelial precursor cells (EPCs) in type 2 diabetes mellitus (T2DM). Metformin exhibits potential for the improvement of endothelial function and the wound healing process. However, the...

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Autores principales: Han, Xue, Tao, Yulong, Deng, Yaping, Yu, Jiawen, Sun, Yuannan, Jiang, Guojun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779947/
https://www.ncbi.nlm.nih.gov/pubmed/28990070
http://dx.doi.org/10.3892/mmr.2017.7707
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author Han, Xue
Tao, Yulong
Deng, Yaping
Yu, Jiawen
Sun, Yuannan
Jiang, Guojun
author_facet Han, Xue
Tao, Yulong
Deng, Yaping
Yu, Jiawen
Sun, Yuannan
Jiang, Guojun
author_sort Han, Xue
collection PubMed
description Wound healing impairment is increasingly recognized to be a consequence of hyperglycemia-induced dysfunction of endothelial precursor cells (EPCs) in type 2 diabetes mellitus (T2DM). Metformin exhibits potential for the improvement of endothelial function and the wound healing process. However, the underlying mechanisms for the observed beneficial effects of metformin application remain to be completely understood. The present study assessed whether metformin, a widely used therapeutic drug for T2DM, may accelerate wound closure in T2DM db/db mice. Genetically hyperglycemic db/db mice were used as the T2DM model. Metformin (250 mg/kg/day; intragastric) was administered for two weeks prior to EPC collection and wound model creation in db/db mice. Wound healing was evaluated by alterations in the wound area and the number of platelet endothelial cell adhesion molecule-positive cells. The function of the isolated bone marrow-derived EPCs (BM-EPCs) was assessed by a tube formation assay. The number of circulating EPCs, and the levels of intracellular nitric oxide (NO) and superoxide (O(2)(−)) were detected by flow cytometry. Thrombospondin-1 (TSP-1) expression was determined by western blot analysis. It was observed that treatment with metformin accelerated wound healing, improved angiogenesis and increased the circulating EPC number in db/db mice. In vitro, treatment with metformin reversed the impaired BM-EPC function reflected by tube formation, and significantly increased NO production while decreasing O(2)(−) levels in BM-EPCs from db/db mice. In addition, TSP-1 expression was markedly attenuated by treatment with metformin in cultured BM-EPCs. Metformin contributed to wound healing and improved angiogenesis in T2DM mice, which was, in part, associated with stimulation of NO, and inhibition of O(2)(−) and TSP-1 in EPCs from db/db mice.
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spelling pubmed-57799472018-02-12 Metformin accelerates wound healing in type 2 diabetic db/db mice Han, Xue Tao, Yulong Deng, Yaping Yu, Jiawen Sun, Yuannan Jiang, Guojun Mol Med Rep Articles Wound healing impairment is increasingly recognized to be a consequence of hyperglycemia-induced dysfunction of endothelial precursor cells (EPCs) in type 2 diabetes mellitus (T2DM). Metformin exhibits potential for the improvement of endothelial function and the wound healing process. However, the underlying mechanisms for the observed beneficial effects of metformin application remain to be completely understood. The present study assessed whether metformin, a widely used therapeutic drug for T2DM, may accelerate wound closure in T2DM db/db mice. Genetically hyperglycemic db/db mice were used as the T2DM model. Metformin (250 mg/kg/day; intragastric) was administered for two weeks prior to EPC collection and wound model creation in db/db mice. Wound healing was evaluated by alterations in the wound area and the number of platelet endothelial cell adhesion molecule-positive cells. The function of the isolated bone marrow-derived EPCs (BM-EPCs) was assessed by a tube formation assay. The number of circulating EPCs, and the levels of intracellular nitric oxide (NO) and superoxide (O(2)(−)) were detected by flow cytometry. Thrombospondin-1 (TSP-1) expression was determined by western blot analysis. It was observed that treatment with metformin accelerated wound healing, improved angiogenesis and increased the circulating EPC number in db/db mice. In vitro, treatment with metformin reversed the impaired BM-EPC function reflected by tube formation, and significantly increased NO production while decreasing O(2)(−) levels in BM-EPCs from db/db mice. In addition, TSP-1 expression was markedly attenuated by treatment with metformin in cultured BM-EPCs. Metformin contributed to wound healing and improved angiogenesis in T2DM mice, which was, in part, associated with stimulation of NO, and inhibition of O(2)(−) and TSP-1 in EPCs from db/db mice. D.A. Spandidos 2017-12 2017-10-04 /pmc/articles/PMC5779947/ /pubmed/28990070 http://dx.doi.org/10.3892/mmr.2017.7707 Text en Copyright: © Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Han, Xue
Tao, Yulong
Deng, Yaping
Yu, Jiawen
Sun, Yuannan
Jiang, Guojun
Metformin accelerates wound healing in type 2 diabetic db/db mice
title Metformin accelerates wound healing in type 2 diabetic db/db mice
title_full Metformin accelerates wound healing in type 2 diabetic db/db mice
title_fullStr Metformin accelerates wound healing in type 2 diabetic db/db mice
title_full_unstemmed Metformin accelerates wound healing in type 2 diabetic db/db mice
title_short Metformin accelerates wound healing in type 2 diabetic db/db mice
title_sort metformin accelerates wound healing in type 2 diabetic db/db mice
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779947/
https://www.ncbi.nlm.nih.gov/pubmed/28990070
http://dx.doi.org/10.3892/mmr.2017.7707
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