College of Pharmacy, Beihua University, Jilin, Jilin 132013, PR China; College of Basic Medical Sciences, Changchun University of Chinese Medicine, Changchun, Jilin 130117, PR China.
College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130117, PR China.
Fitoterapia. 2014 Jun;95:58-64. doi: 10.1016/j.fitote.2014.02.017. Epub 2014 Mar 5.
Compound K (CK) is a final metabolite of panaxadiol ginsenosides from Panax ginseng. Although anti-diabetic activity of CK has been reported in recent years, the molecular mechanism of CK in the treatment of diabetes mellitus remains unclear. In the present investigation, we established a rat model of type 2 diabetes mellitus (T2DM) with insulin resistance using high-fat diet (HFD) and streptozotocin (STZ), and attempted to verify more details and exact mechanisms in the treatment of T2DM. CK was administered orally at three doses [300, 100 and 30 mg/kg bodyweight (b.w.)] to the diabetic rats. Bodyweight, food-intake, fasting blood glucose (FBG), fasting serum insulin (FINS), insulin sensitivity (ISI), total glycerin (TG), total cholesterol (TC), as well as oral glucose tolerance test (OGTT) were evaluated in normal and diabetic rats. According to our results, CK could improve bodyweight and food-intake of diabetic rats. CK exhibited dose-dependent reduction of FBG, TG and TC of diabetic rats. CK treatment also enhanced FINS and ISI. Meanwhile, the glucose tolerance observed in the present study was improved significantly by CK. It is concluded from the results that CK may have improving effects on hyperglycemia and insulin resistance of diabetic rats. Furthermore, research showed that CK could promote the expression of InsR, IRS1, PI3Kp85, pAkt and Glut4 in skeletal muscle tissue of diabetic rats. These results indicate that the hypoglycemic activity of CK is mediated by improvement of insulin sensitivity, which is closely related to PI3K/Akt signaling pathway.
化合物 K（CK）是人参二醇型人参皂苷的最终代谢产物。近年来，虽然有报道称 CK 具有抗糖尿病活性，但 CK 治疗糖尿病的分子机制尚不清楚。在本研究中，我们使用高脂肪饮食（HFD）和链脲佐菌素（STZ）建立了胰岛素抵抗的 2 型糖尿病（T2DM）大鼠模型，并试图更详细和准确地验证其在 T2DM 治疗中的机制。我们以 300、100 和 30mg/kg 体重（b.w.）的剂量给糖尿病大鼠口服 CK。在正常和糖尿病大鼠中评估体重、摄食量、空腹血糖（FBG）、空腹血清胰岛素（FINS）、胰岛素敏感性（ISI）、总甘油三酯（TG）、总胆固醇（TC）以及口服葡萄糖耐量试验（OGTT）。根据我们的结果，CK 可以改善糖尿病大鼠的体重和摄食量。CK 呈剂量依赖性降低糖尿病大鼠的 FBG、TG 和 TC。CK 治疗还增强了 FINS 和 ISI。同时，本研究中观察到的葡萄糖耐量明显改善。由此得出结论，CK 可能对糖尿病大鼠的高血糖和胰岛素抵抗具有改善作用。此外，研究表明 CK 可以促进糖尿病大鼠骨骼肌组织中 InsR、IRS1、PI3Kp85、pAkt 和 Glut4 的表达。这些结果表明，CK 的降血糖活性是通过改善胰岛素敏感性介导的，这与 PI3K/Akt 信号通路密切相关。
