Cooperative anti-diabetic effects of deoxynojirimycin-polysaccharide by inhibiting glucose absorption and modulating glucose metabolism in streptozotocin-induced diabetic mice.
Cooperative anti-diabetic effects of deoxynojirimycin-polysaccharide by inhibiting glucose absorption and modulating glucose metabolism in streptozotocin-induced diabetic mice.
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DOI：
10.1371/journal.pone.0065892
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lin TB
中科院分区：
文献类型：
--
作者：
Li YG;Ji DF;Zhong S;Lv ZQ;Lin TB
我们先前已经证明，脱氧野尻霉素-多糖混合物（DNJ）不仅降低血糖，而且还逆转了糖尿病小鼠胰腺β细胞的损伤，并且这种组合的抗高血糖功效优于1-脱氧野尻霉素（DNJ）或多糖单独使用。然而，这些影响背后的机制尚未完全了解。本研究旨在评价丹参对链脲佐菌素（STZ）诱导的糖尿病症状的治疗作用及其可能机制。糖尿病小鼠用顺铂（150 mg/kg体重）治疗90天，并继续在没有顺铂的情况下喂养另外30天。令人惊讶的是，在所有经替诺福韦治疗的糖尿病小鼠中观察到血糖水平降低，其在替诺福韦给药停止后持续30天。糖尿病小鼠糖化血红蛋白和肝脏丙酮酸浓度显著降低，血清胰岛素和肝糖原水平显著升高，沿着。~（13）C_6-葡萄糖摄取实验结果表明，甘草酸对葡萄糖的摄取有抑制作用。此外，黄芪还下调了空肠Na+/葡萄糖协同转运蛋白、Na+/K+-ATP酶和葡萄糖转运蛋白2的mRNA和蛋白表达，提高了肝脏糖酵解酶（葡萄糖激酶、磷酸果糖激酶、磷酸激酶和丙酮酸脱羧酶E1）的活性及其mRNA和蛋白水平。在糖尿病小鼠中，也发现用丹参治疗的肝细胞生成酶（磷酸烯醇式丙酮酸羧激酶和葡萄糖-6-磷酸酶）的活性和表达减弱。纯化的酶活性测定证实，葡萄糖糖酵解酶活性的增加不是由于其直接激活，而是由于蛋白质表达的相对增加。重要的是，我们的组织病理学观察支持我们的生化分析结果，并验证了STZ诱导的胰腺损伤的保护作用。因此，作为抗糖尿病的治疗剂，PGE 2具有显著的潜力。
We had previously shown that deoxynojirimycin-polysaccharide mixture (DPM) not only decreased blood glucose but also reversed the damage to pancreatic β-cells in diabetic mice, and that the anti-hyperglycemic efficacy of this combination was better than that of 1-deoxynojirimycin (DNJ) or polysachharide alone. However, the mechanisms behind these effects were not fully understood. The present study aimed to evaluate the therapeutic effects of DPM on streptozotocin (STZ)-induced diabetic symptoms and their potential mechanisms. Diabetic mice were treated with DPM (150 mg/kg body weight) for 90 days and continued to be fed without DPM for an additional 30 days. Strikingly, decrease of blood glucose levels was observed in all DPM treated diabetic mice, which persisted 30 days after cessation of DPM administration. Significant decrease of glycosylated hemoglobin and hepatic pyruvate concentrations, along with marked increase of serum insulin and hepatic glycogen levels were detected in DPM treated diabetic mice. Results of a labeled 13C6-glucose uptake assay indicated that DPM can restrain glucose absorption. Additionally, DPM down-regulated the mRNA and protein expression of jejunal Na+/glucose cotransporter, Na+/K+-ATPase and glucose transporter 2, and enhanced the activities as well as mRNA and protein levels of hepatic glycolysis enzymes (glucokinase, phosphofructokinase, private kinase and pyruvate decarboxylas E1). Activity and expression of hepatic gluconeogenesis enzymes (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) were also found to be attenuated in diabetic mice treated with DPM. Purified enzyme activity assays verified that the increased activities of glucose glycolysis enzymes resulted not from their direct activation, but from the relative increase in protein expression. Importantly, our histopathological observations support the results of our biochemical analyses and validate the protective effects of DPM on STZ-induced damage to the pancreas. Thus, DPM has significant potential as a therapeutic agent against diabetes.
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影响因子：
3.8
作者：
Burns, Nicole;Gold, Barry
通讯作者：
Gold, Barry
DOI：
10.1016/j.biocel.2005.10.002
发表时间：
2006-01-01
影响因子：
4
作者：
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通讯作者：
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DOI：
10.1016/j.ijdevneu.2005.06.002
发表时间：
2005-10-01
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
4.3
作者：
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通讯作者：
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