Resveratrol protects against diabetes‐induced endothelial dysfunction in high‐fat diet fed mice

Abstract

Epidemiological studies have shown that red wine consumption is associated with reduced in cardiovascular mortality in the general population and diabetic patients. The present study was designed to investigate whether resveratrol (RSV, a red wine antioxidant) can attenuate diabetes progression, improves diabetes‐related vescular endothelial dysfunctions, and delineated further its underlying mechanisms.Male C57Bl/6 mice were fed with high‐fat diet (HFD) for 17 weeks. Animals developed type 2 diabetes characterized by elevated body weight, hyperglycemia, hyperinsulinemia, and hyperlipidemia. Oral gavage fed with RSV (5 or 10 mg/kg/day for 17 weeks) significantly reduced body weight, plasma glucose, insulin, and triglyceride compared to non‐treated HFD mice. RSV treatment also attenuated plasma glucose elevation and improved insulin responses during glucose tolerance test. Furthermore, HFD diabetic mice exhibited an increasing the numbers of leukocyte rolling, adhering, and transmigrating in the post‐capillary venules of cremaster muscle. In contrast, treatment of RSV significantly attenuated leukocyte rolling, adhesion, and transmigration in HFD diabetic mice. The phenylephrine (PE)‐induced vasoconstriction was dramatically attenuated in HFD diabetic mice; whereas, RSV treatment significantly improved the vessel responsiveness to PE. Our result also shows that the phosphorylated AMPK (5′AMP‐activated protein kinase), Akt, and eNOS (endothelial nitric oxide synthase) protein levels were significantly reduced in aorta of HFD mice. Consistence with the observation on improvement of blood vessel responsiveness, RSV also elevated AMPK, Akt, and eNOS protein phosphorylation levels. Taking together, these results indicate that RSV attenuated diabetes‐related vascular endothelial dysfunctions, at least in part, by elevation of AMPK, Akt, and eNOS proteins phosphorylation.