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d-chiro-Inositol Ameliorates High Fat Diet-Induced Hepatic Steatosis and Insulin Resistance via PKCε-PI3K/AKT Pathway
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2019-05-08 00:00:00 , DOI: 10.1021/acs.jafc.9b01253 Feier Cheng 1 , Lin Han 1 , Yao Xiao 1 , Chuanying Pan 2 , Yunlong Li 3 , Xinhui Ge 1 , Yao Zhang 1 , Shaoqing Yan 1 , Min Wang 1, 4
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2019-05-08 00:00:00 , DOI: 10.1021/acs.jafc.9b01253 Feier Cheng 1 , Lin Han 1 , Yao Xiao 1 , Chuanying Pan 2 , Yunlong Li 3 , Xinhui Ge 1 , Yao Zhang 1 , Shaoqing Yan 1 , Min Wang 1, 4
Affiliation
d-chiro-Inositol (DCI) is a biologically active component found in tartary buckwheat, which can reduce hyperglycemia and ameliorate insulin resistance. However, the mechanism underlying the antidiabetic effects of DCI remains largely unclear. This study investigated the effects and underlying molecular mechanisms of DCI on hepatic gluconeogenesis in mice fed a high fat diet and saturated palmitic acid-treated hepatocytes. DCI attenuated free fatty acid uptake by the liver via lipid trafficking inhibition, reduced diacylglycerol deposition, and hepatic PKCε translocation. Thus, DCI could improve insulin sensitivity by suppressing hepatic gluconeogenesis. Subsequent analyses revealed that DCI decreased hepatic glucose output and the expression levels of PEPCK and G6 Pase in insulin resistant mice through PKCε-IRS/PI3K/AKT signaling pathway. Likewise, such effects of DCI were confirmed in HepG2 cells with palmitate-induced insulin resistance. These findings indicate a novel pathway by which DCI prevents hepatic gluconeogenesis, reduces lipid deposition, and ameliorates insulin resistance via regulation of PKCε-PI3K/AKT axis.
中文翻译:
d-手性肌醇通过PKCε-PI3K/ AKT途径改善高脂饮食诱导的肝脂肪变性和胰岛素抵抗
d -手性肌醇(DCI)是在苦荞麦发现了生物活性组分,它可以减少高血糖和改善胰岛素抵抗。但是,DCI的抗糖尿病作用的基本机制仍不清楚。这项研究调查了DCI对高脂饮食和饱和棕榈酸处理的肝细胞喂养的小鼠肝糖异生的影响及其潜在的分子机制。DCI通过抑制脂质运输,减少二酰基甘油沉积和肝PKCε易位,降低了肝脏对游离脂肪酸的吸收。因此,DCI可通过抑制肝糖异生而改善胰岛素敏感性。随后的分析显示DCI降低了肝葡萄糖输出量,降低了PEPCK和PEPCK的表达水平。通过PKCε-IRS/ PI3K / AKT信号通路的胰岛素抵抗小鼠中的G6酶。同样,在棕榈酸酯诱导的胰岛素抵抗的HepG2细胞中证实了DCI的这种作用。这些发现表明DCI可以通过调节PKCε-PI3K/ AKT轴来防止肝脏糖异生,减少脂质沉积并改善胰岛素抵抗的新途径。
更新日期:2019-05-08
中文翻译:
d-手性肌醇通过PKCε-PI3K/ AKT途径改善高脂饮食诱导的肝脂肪变性和胰岛素抵抗
d -手性肌醇(DCI)是在苦荞麦发现了生物活性组分,它可以减少高血糖和改善胰岛素抵抗。但是,DCI的抗糖尿病作用的基本机制仍不清楚。这项研究调查了DCI对高脂饮食和饱和棕榈酸处理的肝细胞喂养的小鼠肝糖异生的影响及其潜在的分子机制。DCI通过抑制脂质运输,减少二酰基甘油沉积和肝PKCε易位,降低了肝脏对游离脂肪酸的吸收。因此,DCI可通过抑制肝糖异生而改善胰岛素敏感性。随后的分析显示DCI降低了肝葡萄糖输出量,降低了PEPCK和PEPCK的表达水平。通过PKCε-IRS/ PI3K / AKT信号通路的胰岛素抵抗小鼠中的G6酶。同样,在棕榈酸酯诱导的胰岛素抵抗的HepG2细胞中证实了DCI的这种作用。这些发现表明DCI可以通过调节PKCε-PI3K/ AKT轴来防止肝脏糖异生,减少脂质沉积并改善胰岛素抵抗的新途径。