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Metformin restores endothelial function in aorta of diabetic rats.


ABSTRACT:

Background and purpose

The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been fully elucidated. This study was designed to assess the effect of metformin on impaired endothelial function, oxidative stress, inflammation and advanced glycation end products formation in type 2 diabetes mellitus.

Experimental approach

Goto-Kakizaki (GK) rats, an animal model of nonobese type 2 diabetes, fed with normal and high-fat diet during 4 months were treated with metformin for 4 weeks before evaluation. Systemic oxidative stress, endothelial function, insulin resistance, nitric oxide (NO) bioavailability, glycation and vascular oxidative stress were determined in the aortic rings of the different groups. A pro-inflammatory biomarker the chemokine CCL2 (monocyte chemoattractant protein-1) was also evaluated.

Key results

High-fat fed GK rats with hyperlipidaemia showed increased vascular and systemic oxidative stress and impaired endothelial-dependent vasodilatation. Metformin treatment significantly improved glycation, oxidative stress, CCL2 levels, NO bioavailability and insulin resistance and normalized endothelial function in aorta.

Conclusion and implications

Metformin restores endothelial function and significantly improves NO bioavailability, glycation and oxidative stress in normal and high-fat fed GK rats. This supports the concept of the central role of metformin as a first-line therapeutic to treat diabetic patients in order to protect against endothelial dysfunction associated with type 2 diabetes mellitus.

SUBMITTER: Sena CM 

PROVIDER: S-EPMC3087142 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Metformin restores endothelial function in aorta of diabetic rats.

Sena Cristina M CM   Matafome Paulo P   Louro Teresa T   Nunes Elsa E   Fernandes Rosa R   Seiça Raquel M RM  

British journal of pharmacology 20110501 2


<h4>Background and purpose</h4>The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been fully elucidated. This study was designed to assess the effect of metformin on impaired endothelial function, oxidative stress, inflammation and advanced glycation end products formation in type 2 diabetes mellitus.<h4>Experimental approach</h4>Goto-Kakizaki (GK) rats, an animal model of nonobese type 2 diabetes, fed with normal and high-fat diet  ...[more]

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