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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2016

Open Access 01-12-2016 | Original investigation

Metformin improves the angiogenic functions of endothelial progenitor cells via activating AMPK/eNOS pathway in diabetic mice

Authors: Jia-Wen Yu, Ya-Ping Deng, Xue Han, Guo-Fei Ren, Jian Cai, Guo-Jun Jiang

Published in: Cardiovascular Diabetology | Issue 1/2016

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Abstract

Background

Endothelial dysfunction has been suggested as a possible causal link between hyperglycemia and microvascular complications in diabetes mellitus. The effect of metformin on endothelial progenitor cells (EPCs) is still unclear. This study was designed to test the hypothesis that metformin could accelerate wound healing by improving the impaired EPC functions in streptozotocin-induced diabetic mice.

Methods

Streptozotocin (STZ, 60 mg/kg/d × 5 d, i.p.) was injected to induce type 1 diabetes in male C57BL/6 mice. Mice were treated with metformin (250 mg/kg/d, i.g.) for consecutive 14 days. Wound closure was evaluated by wound area and number of CD31 stained capillaries. Functions of bone marrow-endothelial progenitor cells (BM-EPCs) were assessed by tube formation and migration assays, and expression of AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) was determined by western blot analysis.

Results

Metformin accelerated wound closure and stimulated angiogenesis in diabetic mice. The number of circulating EPCs was increased significantly in metformin treated diabetic mice. Abilities of tube formation and migration of BM-EPCs were impaired in diabetic mice, which were improved by metformin. Expression of both phosphorylated-AMPK and phosphorylated-eNOS was significantly increased, and nitric oxide (NO) production was enhanced by metformin in BM-EPCs of diabetic mice. In vitro, metformin improved impaired BM-EPC functions, and increased phosphorylated-eNOS expression and NO production in cultured BM-EPCs caused by high glucose, which was prevented by the AMPK inhibitor compound C.

Conclusions

Our results suggest that metformin could improve BM-EPC functions in STZ-induced diabetic mice, which was possibly dependent on the AMPK/eNOS pathway.
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Available only for authorised users
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Metadata
Title
Metformin improves the angiogenic functions of endothelial progenitor cells via activating AMPK/eNOS pathway in diabetic mice
Authors
Jia-Wen Yu
Ya-Ping Deng
Xue Han
Guo-Fei Ren
Jian Cai
Guo-Jun Jiang
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2016
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-016-0408-3

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