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索诺拉忍冬(葫芦科)通过激活非 PI3K 依赖途径诱导人脂肪细胞的葡萄糖摄取。

Ibervillea sonorae (Cucurbitaceae) induces the glucose uptake in human adipocytes by activating a PI3K-independent pathway.

机构信息

Instituto Potosino de Investigación Científica y Tecnológica, División de Biología Molecular, Camino a la presa San José 2055, Lomas 4a secc., San Luis Potosí 76216, Mexico.

Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Querétaro, Mexico.

出版信息

J Ethnopharmacol. 2014 Mar 28;152(3):546-52. doi: 10.1016/j.jep.2014.01.041. Epub 2014 Feb 15.

DOI:10.1016/j.jep.2014.01.041
PMID:24534528
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Ibervillea sonorae (S. Watson) Greene (Cucurbitaceae), a plant used for the empirical treatment of type 2 diabetes in México, exerts antidiabetic effects on animal models but its mechanism of action remains unknown. The aim of this study is to investigate the antidiabetic mechanism of an Ibervillea sonorae aqueous extract (ISE).

MATERIALS AND METHODS

Non-toxic ISE concentrations were assayed on the glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes, both in the absence or the presence of insulin signaling pathway inhibitors, and on murine and human adipogenesis. Chemical composition of ISE was examined by spectrophotometric and HPLC techniques.

RESULTS

ISE stimulated the 2-NBDGlucose uptake by mature adipocytes in a concentration-dependent manner. ISE 50 µg/ml induced the 2-NBDG uptake in insulin-sensitive 3T3-F442A, 3T3-L1 and human adipocytes by 100%, 63% and 33%, compared to insulin control. Inhibitors for the insulin receptor, PI3K, AKT and GLUT4 blocked the 2-NBDG uptake in murine cells, but human adipocytes were insensitive to the PI3K inhibitor Wortmannin. ISE 50 µg/ml also stimulated the 2-NBDG uptake in insulin-resistant adipocytes by 117% (3T3-F442A), 83% (3T3-L1) and 48% (human). ISE induced 3T3-F442A adipogenesis but lacked proadipogenic effects on 3T3-L1 and human preadipocytes. Chemical analyses showed the presence of phenolics in ISE, mainly an appreciable concentration of gallic acid.

CONCLUSION

Ibervillea sonorae exerts its antidiabetic properties by means of hydrosoluble compounds stimulating the glucose uptake in human preadipocytes by a PI3K-independent pathway and without proadipogenic effects.

摘要

民族药理学相关性

Ibervillea sonorae(S. Watson)Greene(葫芦科),一种在墨西哥用于经验性治疗 2 型糖尿病的植物,对动物模型具有抗糖尿病作用,但作用机制尚不清楚。本研究旨在探讨Ibervillea sonorae 水提物(ISE)的抗糖尿病机制。

材料和方法

在不存在或存在胰岛素信号通路抑制剂的情况下,测定了无毒ISE 浓度对胰岛素敏感和胰岛素抵抗的鼠和人培养脂肪细胞葡萄糖摄取的影响,以及对鼠和人脂肪生成的影响。通过分光光度法和 HPLC 技术检查了 ISE 的化学成分。

结果

ISE 以浓度依赖的方式刺激成熟脂肪细胞的 2-NBDGlucose 摄取。ISE 50μg/ml 分别使胰岛素敏感的 3T3-F442A、3T3-L1 和人脂肪细胞中的 2-NBDG 摄取增加 100%、63%和 33%,与胰岛素对照相比。胰岛素受体、PI3K、AKT 和 GLUT4 的抑制剂阻断了鼠细胞中的 2-NBDG 摄取,但人脂肪细胞对 PI3K 抑制剂 Wortmannin 不敏感。ISE 50μg/ml 还使胰岛素抵抗的脂肪细胞中的 2-NBDG 摄取增加了 117%(3T3-F442A)、83%(3T3-L1)和 48%(人)。ISE 诱导 3T3-F442A 脂肪生成,但对 3T3-L1 和人前脂肪细胞没有促脂肪生成作用。化学分析表明 ISE 中存在酚类化合物,主要是相当可观浓度的没食子酸。

结论

Ibervillea sonorae 通过水溶性化合物发挥其抗糖尿病特性,通过一种不依赖于 PI3K 的途径刺激人前脂肪细胞的葡萄糖摄取,并且没有促脂肪生成作用。

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