Hypoglycemic effect of protopanaxadiol-type ginsenosides and compound K on Type 2 Diabetes mice induced by High-Fat Diet combining with Streptozotocin via suppression of hepatic gluconeogenesis
Hypoglycemic effect of protopanaxadiol-type ginsenosides and compound K on Type 2 Diabetes mice induced by High-Fat Diet combining with Streptozotocin via suppression of hepatic gluconeogenesis
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DOI：
10.1016/j.fitote.2011.10.011
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发表时间：
2012-01-01
期刊：
影响因子：
3.4
通讯作者：
Yang, Geng-Liang
中科院分区：
文献类型：
--
作者：
Li, Wei;Zhang, Ming;Yang, Geng-Liang
化合物 K (CK) 是人参中原人参二醇型人参皂苷 (PDG) 的最终肠道代谢产物。尽管近年来在遗传小鼠模型（db/db 小鼠）中报道了 CK 的抗糖尿病活性，但 CK 和 PDG 在 2 型糖尿病（一种更常见的糖尿病形式）中的治疗作用仍不清楚。在本研究中，我们开发了一种非胰岛素依赖型糖尿病小鼠，它密切模拟了人类疾病的代谢异常。为此，通过联合链脲佐菌素在雄性 ICR 小鼠中诱导 2 型糖尿病。 HFD喂养4周的雄性ICR小鼠腹腔注射100mg/kg的STZ。 4周后，将空腹（12小时）血糖水平（FBG）高于7.8 mmol/L的小鼠分为3组（n = 12），并用载体（糖尿病模型，DM）、300 mg/kg/天的PDG和30 mg/kg/天的CK治疗4周，同时继续高脂肪饮食。 FBG 水平一致证明了 CK 和 PDG 的降血糖作用，并且在口服葡萄糖耐量试验 (OGTT) 期间观察到胰岛素增敏作用。此外，还研究了2型糖尿病小鼠的降血糖作用机制。糖异生基因、磷酸烯醇丙酮酸羧激酶 (PEPCK) 和葡萄糖 6 磷酸酶 (G6Pase) 在两个治疗组中均有所减少，其中 CK 的影响更大。这些发现证明了 CK 通过下调肝脏中 PEPCK 和 G6Pase 的表达，对 HFD/STZ 诱导的 2 型糖尿病具有降血糖和胰岛素增敏作用。 (C) 2011 Elsevier B.V. 保留所有权利。
Compound K (CK) is a final intestinal metabolite of protopanaxadiol-type ginsenosides (PDG) from Panax ginseng. Although anti-diabetic activity of CK have been reported with genetic mouse models (db/db mice) in recent years, the therapeutic usefulness of CK and PDG in type 2 diabetes, a more prevalent form of diabetes, remains unclear. In the present investigation, we developed a mouse of non-insulin-dependent diabetes mellitus that closely simulated the metabolic abnormalities of the human disease. For this purpose, type 2 diabetes was induced in male ICR mice by combining of streptozotocin. The male ICR mice fed with HFD for 4 weeks received 100 mg/kg of STZ injected intraperitoneally. After 4 weeks, mice with fasting (12 h) blood glucose levels (FBG) above 7.8 mmol/L were divided into 3 groups (n = 12) and treated with vehicle (diabetes model, DM), 300 mg/kg/day of PDG and 30 mg/kg/day of CK for 4 weeks while continuing on the high-fat diet. Hypoglycemic effects of CK and PDG were consistently demonstrated by FBG levels, and insulin-sensitizing effects were seen during oral glucose tolerance testing (OGTT). Moreover, the mechanism of hypoglycemic effect in type 2 diabetic mice was examined. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase), were decreased in two treatment groups with CK showing greater effects. These findings demonstrated the hypoglycemic and insulin-sensitizing capabilities of CK on type 2 diabetes induced by HFD/STZ via down-regulation of PEPCK and G6Pase expression in liver. (C) 2011 Elsevier B.V. All rights reserved.