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二型糖尿病大鼠中,白杨素通过过氧化物酶体增殖物激活受体-γ和 PI3K/Akt 信号通路发挥抗糖尿病作用。

Antidiabetic activity of eupafolin through peroxisome proliferator-activated receptor-gamma and PI3K/Akt signaling in Type 2 diabetic rats.

机构信息

Department of General Medicine, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang City, Jiangxi Province, China.

Department of Geriatrics, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang City, Jiangxi Province, China.

出版信息

J Biochem Mol Toxicol. 2023 Nov;37(11):e23463. doi: 10.1002/jbt.23463. Epub 2023 Aug 11.

DOI:10.1002/jbt.23463
PMID:37566541
Abstract

Eupafolin is a phyto compound of flavone that exerts anti-inflammatory, antioxidant, and antiproliferative properties. The main purpose of this study is to examine the antidiabetic effect of eupafolin on nicotinamide-streptozotocin (STZ)-induced Type 2 diabetes (T2D) rats. After nicotinamide (120 mg/kg) treatment, STZ (60 mg/kg) was administrated intravenously to induce T2D. Rats with fasting blood glucose (FBG) > 200 mg/dL are chosen for the study 7 days after T2D induction. The eupafolin treatment was continued for another 15 days. FBG and an oral glucose tolerance test (OGTT) were measured on the 21st day after T2D induction. The blood lipid, serum insulin, and homeostatic model assessment (HOMA-IR) were determined. In liver homogenate, oxidative stress indicators were measured. In addition, the effect of eupafolin on the expression of the proteins InsR, insulin receptor substrate (IRS)-2, GLUT4, PPARγ, and phosphatidylinositol 3-kinase (PI3K)/Akt was investigated using a western blot. As measured by OGTT and HOMA-IR, eupafolin treatment reduced FBG and insulin resistance (IR). Furthermore, when compared to diabetic rats, liver antioxidant enzymes were dramatically normalized. The level of glycogen in the liver of diabetic rats was increased by eupafolin treatment. In T2D rats, eupafolin dramatically increased the InsR, IRS-2, GLUT4, and PPARγ. Further, the eupafolin treatment activated the PI3K/Akt signaling in T2D rats. These findings imply that the antidiabetic mechanism of eupafolin may be related to the activation of the PPARγ and the PI3K/Akt signaling pathway in T2D rats. As a result, the flavonoid eupafolin could be an antidiabetic medication for T2D after a comprehensive clinical investigation.

摘要

柚皮苷是一种类黄酮植物化合物,具有抗炎、抗氧化和抗增殖作用。本研究的主要目的是研究柚皮苷对烟酰胺-链脲佐菌素(STZ)诱导的 2 型糖尿病(T2D)大鼠的降糖作用。烟酰胺(120mg/kg)处理后,静脉注射 STZ(60mg/kg)诱导 T2D。T2D 诱导后 7 天,选择空腹血糖(FBG)>200mg/dL 的大鼠进行研究。柚皮苷治疗继续进行 15 天。T2D 诱导后第 21 天测量 FBG 和口服葡萄糖耐量试验(OGTT)。测定血脂、血清胰岛素和稳态模型评估(HOMA-IR)。在肝匀浆中测定氧化应激指标。此外,还通过 Western blot 研究了柚皮苷对胰岛素受体(InsR)、胰岛素受体底物(IRS)-2、GLUT4、过氧化物酶体增殖物激活受体γ(PPARγ)和磷酸肌醇 3-激酶(PI3K)/蛋白激酶 B(Akt)表达的影响。如 OGTT 和 HOMA-IR 所示,柚皮苷治疗可降低 FBG 和胰岛素抵抗(IR)。此外,与糖尿病大鼠相比,肝抗氧化酶明显正常化。柚皮苷治疗可增加糖尿病大鼠肝糖原含量。在 T2D 大鼠中,柚皮苷显著增加 InsR、IRS-2、GLUT4 和 PPARγ。此外,柚皮苷治疗可激活 T2D 大鼠的 PI3K/Akt 信号通路。这些发现表明,柚皮苷的降糖机制可能与 T2D 大鼠中 PPARγ 和 PI3K/Akt 信号通路的激活有关。因此,黄酮类柚皮苷在经过全面的临床研究后,可能成为治疗 T2D 的药物。

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