Ginsenoside Rb2 promotes glucose metabolism and attenuates fat accumulation via AKT-dependent mechanisms
Ginsenoside Rb2 promotes glucose metabolism and attenuates fat accumulation via AKT-dependent mechanisms
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DOI：
10.1016/j.biopha.2018.01.111
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发表时间：
2018-04-01
影响因子：
7.5
通讯作者：
Gu, Xuejiang
中科院分区：
文献类型：
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作者：
Dai, Shanshan;Hong, Yilian;Gu, Xuejiang
人参皂苷是人参的主要活性成分，已被证明具有抗糖尿病、抗炎等作用。人参皂苷Rb2是人参中含量最丰富的皂苷，本研究探讨了人参皂苷Rb2在胰岛素敏感细胞系3T3-L1脂肪细胞和高脂饮食诱导的肥胖小鼠降血糖机制中的作用。测定3T3-L1脂肪细胞的葡萄糖摄取量。检测胰岛素信号转导通路，包括胰岛素AKT、胰岛素受体(IR)β亚基、IR底物(IRS)-1、磷脂酰肌醇3-激酶(PI3K)。用肿瘤坏死因子-α处理的3T3-L1脂肪细胞作为胰岛素抵抗模型，检测p-AKT、c-Jun氨基末端激酶(JNK)、MAPK和核因子(NF)-kappaB信号转导通路。作为体内研究，C57BL/6J小鼠以高脂饲料喂养9周，并添加或不添加Rb2。然后我们研究了Rb2对这些高脂饮食诱导的肥胖小鼠糖代谢的影响。我们的结果表明，Rb2增加了3T3-L1脂肪细胞对葡萄糖的摄取，这不依赖于胰岛素受体β亚基(IRβ)，主要通过胰岛素受体底物(IRS)-1-磷脂酰肌醇3-激酶(PI3K)-AKT/PKB途径。RB2抑制肿瘤坏死因子-α诱导的MAPK和核因子-kappaB信号通路的激活以及炎症因子的表达。在高脂饮食诱导的肥胖小鼠中，Rb2减轻了脂肪质量并调节了胰岛素抵抗。在小鼠脂肪组织中，AKT的Rb2磷酸化与糖代谢相关。此外，Rb2可减轻3T3-L1脂肪细胞的胰岛素抵抗，减少脂肪质量，并改善高脂饮食肥胖小鼠的胰岛素敏感性。
Ginsenosides, the major active constituents of ginseng, have been demonstrated possess anti-diabetic, anti-inflammatory effects. Ginsenoside Rb2 (Rb2) is the most abundant saponin in Panax ginseng, this study investigates the role of Rb2 in the anti-hyperglycemic mechanism of insulin-sensitive cell lines 3T3-L1 adipocytes as well as high fat diet-induced obesity mice. Glucose uptake of 3T3-L1 adipocytes was measured. The insulin signaling cascade, including insulin AKT, insulin receptor (IR) beta-subunit, IR substrate (IRS) -1, phosphatidylinositol 3-kinase (PI3K) were also examined. TNF-alpha-treated 3T3-L1 adipocytes were used as an insulin resistant model in which p-AKT, c-Jun NH2-terminal kinase (JNK), MAPK, and nuclear factor (NF) -kappa B signaling cascades were examined. As an in vivo study, C57BL/6J mice were fed with a high-fat diet for 9 weeks, with or without Rb2 supplementation. Then we investigated the effects of Rb2 on glycometabolism in these high fat diet-induced obesity mice. Our results demonstrate Rb2 increases glucose uptake in 3T3-L1 adipocytes, independent of insulin receptor beta-subunit (IR beta) and principally through the insulin receptor substrate (IRS)-1-phosphatidylinositol 3-kinase (PI3K)-AKT/PKB pathway. Rb2 inhibited TNF-alpha-induced activation of MAPK and nuclear factor (NF)-kappa B signaling pathway as well as the expression of inflammatory factors. In high fat diet-induced obesity mice, Rb2 attenuated fat mass and regulated insulin resistance. In mouse adipose tissue, Rb2 phosphorylation of AKT was correlated with glycometabolism. Furthermore, Rb2 attenuates insulin resistance in 3T3-L1 adipocytes, reduces fat mass, and improves insulin sensitivity in high fat diet-obesity mice.