Arteriosclerosis, thrombosis, and vascular biology
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Arterioscler. Thromb. Vasc. Biol. · Apr 2014
Metformin protects endothelial function in diet-induced obese mice by inhibition of endoplasmic reticulum stress through 5' adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor δ pathway.
5' Adenosine monophosphate-activated protein kinase (AMPK) interacts with peroxisome proliferator-activated receptor δ (PPARδ) to induce gene expression synergistically, whereas the activation of AMPK inhibits endoplasmic reticulum (ER) stress. Whether the vascular benefits of antidiabetic drug metformin (AMPK activator) in diabetes mellitus and obesity is mediated by PPARδ remains unknown. We aim to investigate whether PPARδ is crucial for metformin in ameliorating ER stress and endothelial dysfunction induced by high-fat diet. ⋯ Metformin restores endothelial function through inhibiting ER stress and oxidative stress and increasing NO bioavailability on activation of AMPK/PPARδ pathway in obese diabetic mice.