Metabolomics reveals the protective of Dihydromyricetin on glucose homeostasis by enhancing insulin sensitivity.

Metabolomics reveals the protective of Dihydromyricetin on glucose homeostasis by enhancing insulin sensitivity.
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代谢组学揭示二氢杨梅素通过增强胰岛素敏感性对葡萄糖稳态的保护作用

DOI:
10.1038/srep36184
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发表时间:
2016-10-31
期刊:
影响因子:
4.6
通讯作者:
Xiao P
Xiao P
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Le L;Jiang B;Wan W;Zhai W;Xu L;Hu K;Xiao P

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二氢杨梅素(DMY)是显齿蛇葡萄中一种重要的二氢黄酮,具有抗氧化作用,可改善骨骼肌胰岛素敏感性,并发挥保肝作用。然而,很少有人知道DMY的影响,在高脂饮食(HFD)诱导的肝胰岛素抵抗的背景下。雄性Sprague-Dawley(SD)大鼠喂食补充有DMY的HFD(60%脂肪)8周。对HFD诱导的胰岛素抵抗大鼠给予DMY可降低高血糖症、血浆胰岛素水平和肝脏脂肪变性。此外,DMY治疗调节24个代谢途径,包括葡萄糖代谢,TCA循环。DMY显著增强葡萄糖摄取,并改善葡萄糖转运蛋白1的转位。DMY特异性地促进AMP活化蛋白激酶(AMPK)的磷酸化。此外,高糖暴露可降低胰岛素刺激的Akt 2 Ser 474和胰岛素受体底物1(IRS-1)Ser 612的磷酸化水平,增加GSK-3β磷酸化水平,并上调G6 β和PEPCK表达。总的来说,DMY改善了葡萄糖相关的代谢,同时降低了HFD喂养大鼠的脂质水平。这些数据表明,DMY可能是一种有用的药物,用于治疗2型糖尿病胰岛素抵抗和治疗肝脂肪变性。
Dihydromyricetin (DMY), an important flavanone found in Ampelopsis grossedentata, possesses antioxidative properties that ameliorate skeletal muscle insulin sensitivity and exert a hepatoprotective effect. However, little is known about the effects of DMY in the context of high-fat diet (HFD)-induced hepatic insulin resistance. Male Sprague-Dawley(SD) rats were fed a HFD(60% fat) supplemented with DMY for 8 weeks. The administration of DMY to the rats with HFD-induced insulin resistance reduces hyperglycemia, plasma levels of insulin, and steatosis in the liver. Furthermore, DMY treatment modulated 24 metabolic pathways, including glucose metabolism, the TCA cycle. DMY significantly enhanced glucose uptake and improved the translocation of glucose transporter 1. The specificity of DMY promoted the phosphorylation of AMP-activated protein kinase (AMPK). In addition, the exposure of HepG2 cells to high glucose concentrations impaired the insulin-stimulated phosphorylation of Akt2 Ser474 and insulin receptor substrate-1 (IRS-1) Ser612, increased GSK-3β phosphorylation, and upregulated G6Pase and PEPCK expression. Collectively, DMY improved glucose-related metabolism while reducing lipid levels in the HFD-fed rats. These data suggest that DMY might be a useful drug for use in type 2 diabetes insulin resistance therapy and for the treatment of hepatic steatosis.
DOI: 10.2337/diabetes.54.6.1692
发表时间: 2005-06-01
期刊: DIABETES
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