Liu I-Min, Tzeng Thing-Fong, Liou Shorong-Shii, Lan Ting-Wei
Department of Pharmacy, Tajen University, Yanpu Shiang, Ping Tung Shien, Taiwan, ROC.
Planta Med. 2007 Aug;73(10):1054-60. doi: 10.1055/s-2007-981577. Epub 2007 Aug 13.
In an attempt to develop new substances for treating insulin resistance, obese Zucker rats were employed to screen the effect of myricetin, an active principle of Abelmoschus moschatus (Malvaceae), on insulin resistance. Myricetin purified from the aerial portion of the plant was administered intravenously ( I. V.) into animals. A dose-dependent decrease in the plasma glucose concentration of obese Zucker rats was observed 30 min following an I. V. injection. Moreover, repeated I. V. injection of myricetin (1 mg/kg) into obese Zucker rats 3 times daily for 1 week reduced the value of the glucose-insulin index, an index of insulin resistance calculated from the areas under the curve of glucose and insulin during the intraperitoneal glucose tolerance test. Additionally, repeated myricetin treatments overturned the inability of insulin to increase the expression of glucose transporter subtype 4 (GLUT 4) and to increase the protein levels and phosphorylation of insulin receptor substrate-1 (IRS-1) in soleus muscle of these obese rats. The inability of insulin to increase expression of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase) and to promote Akt serine phosphorylation in soleus muscle of these rats were also overturned by repeated myricetin treatments. These findings indicate that myricetin improves insulin sensitivity through increased post-receptor insulin signaling mediated by enhancements in IRS-1-associated PI3-kinase and GLUT 4 activity in muscles of obese Zucker rats. Myricetin might be used as a model substance for the development of antidiabetic compounds.
为了研发治疗胰岛素抵抗的新物质，利用肥胖 Zucker 大鼠来筛选锦葵科黄蜀葵的活性成分杨梅素对胰岛素抵抗的作用。从植物地上部分纯化得到的杨梅素通过静脉注射给予动物。静脉注射后 30 分钟观察到肥胖 Zucker 大鼠的血浆葡萄糖浓度呈剂量依赖性下降。此外，每天 3 次对肥胖 Zucker 大鼠重复静脉注射杨梅素（1 mg/kg），持续 1 周，降低了葡萄糖 - 胰岛素指数的值，该指数是根据腹腔葡萄糖耐量试验期间葡萄糖和胰岛素曲线下面积计算得出的胰岛素抵抗指标。另外，重复给予杨梅素治疗扭转了胰岛素无法增加这些肥胖大鼠比目鱼肌中葡萄糖转运蛋白 4（GLUT 4）表达以及无法增加胰岛素受体底物 -1（IRS -1）蛋白水平和磷酸化的情况。重复给予杨梅素治疗还扭转了胰岛素无法增加这些大鼠比目鱼肌中磷脂酰肌醇 3 -激酶（PI3 -激酶）的 p85 调节亚基表达以及无法促进 Akt 丝氨酸磷酸化的情况。这些发现表明，杨梅素通过增强肥胖 Zucker 大鼠肌肉中与 IRS -1 相关的 PI3 -激酶和 GLUT 4 活性介导的受体后胰岛素信号传导来改善胰岛素敏感性。杨梅素可能用作开发抗糖尿病化合物的模型物质。
