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Resveratrol ameliorated gestational diabetes through regulation of AMPKmediated NF-kB signaling pathway

Gestational diabetes mellitus is one kind of complications of pregnancy, which influence the health of maternal-child in clinical. Evidences have showed that Resveratrol presents benefits for the treatment of gestational diabetes. However, potential mechanisms of Resveratrol-mediated improvements of glucose and lipid metabolism have not been well understood so far. In this study, we investigated the therapeutic effects and potential mechanism of Resveratrol-mediated treatments for gestational diabetes. We investigated the inflammation, oxidative stress, apoptosis and adenosine monophosphateactivated protein kinase (AMPK) in embryos in embryonic day 16 in a mice model of gestational diabetes induced by streptozotocin. Glucose, insulin resistance and glucose and lipid metabolism were also analyzed in mice model of gestational diabetes after treatment with Resveratrol. Our results showed that Resveratrol treatment significantly decreased inflammatory factors expression, such as IL-1β, IL-6, CRP and TNF-α. Resveratrol (8.0 mg/kg) administration decreased expression levels of SOD, ROS, CAT and GSH in oxidative stress. Apoptosis of pancreatic cells in rats was inhibited by Resveratrol treatment through decreasing pro-apoptosis protein expression and increasing anti-apoptosis protein expression. Results also demonstrated that Resveratrol administration down-regulated AMPK expression and activity, which further inhibited expression levels of p65, Ikkβ and IkBα in embryonic cells. Mechanism analyses demonstrated that Resveratrol inhibited inflammatory pathway of embryonic cells through AMPK-mediated NF-κB signaling pathway. In vivo assays showed that metabolism of glucose and lipid were improved and tolerance of glucose and insulin were meliorated in mice model of gestational diabetes mellitus. In conclusion, these results indicate that resveratrol treatment decreased inflammation, prevented apoptosis, decreased embryonic oxidative stress, improved metabolism of glucose and lipid, and meliorated glucose and insulin levels of gestational diabetes mellitus mice, which suggest Resveratrol may be promising agent for the treatment of diabetic pregnancy.

Author(s): Bo Hong, Xiang Ding, Hongmei Jia, Jianmei Zhang