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.

• Authors: Cristina M Sena, Paulo Matafome, Teresa Louro, Elsa Nunes, Rosa Fernandes, Raquel M Seiça
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 163 Issue 2 Pg. 424-37 (May 2011) ISSN: 1476-5381 [Electronic] England
• PMID: 21250975 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Chemical References

• Biomarkers
• Cell Adhesion Molecules
• Glycation End Products, Advanced
• Hypoglycemic Agents
• Microfilament Proteins
• Phosphoproteins
• vasodilator-stimulated phosphoprotein
• Nitric Oxide
• Metformin

Topics

• Animals
• Aorta (drug effects, metabolism, physiopathology)
• Biomarkers (blood)
• Cell Adhesion Molecules (metabolism)
• Diabetes Mellitus, Type 2 (drug therapy, metabolism, physiopathology)
• Endothelium, Vascular (drug effects, metabolism, physiopathology)
• Glycation End Products, Advanced (metabolism)
• Hypoglycemic Agents (pharmacology)
• Inflammation (metabolism)
• Male
• Metformin (pharmacology)
• Microfilament Proteins (metabolism)
• Nitric Oxide (physiology)
• Oxidative Stress
• Phosphoproteins (metabolism)
• Phosphorylation
• Rats
• Rats, Wistar
• Vasodilation