Metformin restores endothelial function in aorta of diabetic rats.
OBJECTIVE
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.


METHODS
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.


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.


CONCLUSIONS
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.
Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. csena@ci.uc.pt
Cristina M
CM
Sena
Paulo
P
Matafome
Teresa
T
Louro
Elsa
E
Nunes
Rosa
R
Fernandes
Raquel M
RM
Seiça
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008840:Microfilament Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation; D000098662:Vasodilator-Stimulated Phosphoprotein
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D009569:Nitric Oxide; D008687:Metformin
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