桑叶多糖提取物改善高脂饮食和链脲佐菌素诱导的2型糖尿病大鼠的肝脏葡萄糖代谢和胰岛素信号传导。
A polysaccharide extract of mulberry leaf ameliorates hepatic glucose metabolism and insulin signaling in rats with type 2 diabetes induced by high fat-diet and streptozotocin.
作者信息
Ren Chunjiu, Zhang Yao, Cui Weizheng, Lu Guobing, Wang Yanwen, Gao Huiju, Huang Lu, Mu Zhimei
出版信息
Int J Biol Macromol. 2015 Jan;72:951-9. doi: 10.1016/j.ijbiomac.2014.09.060.
Mulberry leaf is a traditional medicine used to treat diabetes in the clinic. The aim of this study was to determine the mechanisms by which mulberry leaf polysaccharide (MLPII), improves hepatic glucose metabolism and insulin resistance in rats with type 2 diabetes induced by high fat and streptozotocin (STZ). MLPII was administered for 6 weeks after establishment of type 2 diabetes in Wistar rats. At the end of the experiment, oral glucose tolerance, liver glycogen content, glucose synthase (GS) activity and insulin resistance were determined. Expression patterns of proteins and genes associated with insulin signaling as well as biomarkers of oxidative stress and antioxidant enzyme activities were assayed. Compared with normal control rats, MLPII treatment significantly improved oral glucose tolerance (P < 0.01) and restored the glycogen level (P < 0.01) and GS activity (P < 0.05) in diabetic rats. Insulin resistance was improved in MLPII-treated diabetic rats (P < 0.01). Furthermore, expression levels of insulin receptor substrate 2 (IRS2), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB/AKT) involved in insulin signaling were significantly increased (P < 0.01), while protein–tyrosine phosphatase 1B (PTP1B) expression was markedly reduced (P < 0.01). The levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) in livers of the MLPII-treated group were significantly reduced (P < 0.01), while activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), were significantly increased (P < 0.01, P < 0.01, P < 0.01, respectively). The results clearly indicate that MLPII treatment effectively normalizes hepatic glucose metabolism and insulin signaling by inhibiting the expression of PTP1B, activating the PI3K–AKT pathway and mitigating oxidative stress in the livers of rats with type 2 diabetes induced by high fat and STZ.
桑叶是临床上用于治疗糖尿病的传统药物。本研究的目的是确定桑叶多糖（MLPII）改善高脂和链脲佐菌素（STZ）诱导的2型糖尿病大鼠肝脏葡萄糖代谢和胰岛素抵抗的机制。在Wistar大鼠建立2型糖尿病后给予MLPII 6周。实验结束时，测定口服葡萄糖耐量、肝糖原含量、葡萄糖合酶（GS）活性和胰岛素抵抗。检测与胰岛素信号相关的蛋白质和基因的表达模式以及氧化应激生物标志物和抗氧化酶活性。与正常对照大鼠相比，MLPII治疗显著改善了糖尿病大鼠的口服葡萄糖耐量（P < 0.01），恢复了糖原水平（P < 0.01）和GS活性（P < 0.05）。MLPII治疗的糖尿病大鼠胰岛素抵抗得到改善（P < 0.01）。此外，参与胰岛素信号传导的胰岛素受体底物2（IRS2）、磷脂酰肌醇3激酶（PI3K）和蛋白激酶B（PKB/AKT）的表达水平显著增加（P < 0.01），而蛋白酪氨酸磷酸酶1B（PTP1B）的表达明显降低（P < 0.01）。MLPII治疗组肝脏中8-羟基-2-脱氧鸟苷（8-OHdG）和丙二醛（MDA）水平显著降低（P < 0.01），而抗氧化酶超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）的活性显著增加（分别为P < 0.01、P < 0.01、P < 0.01）。结果清楚地表明，MLPII治疗通过抑制PTP1B的表达、激活PI3K-AKT途径和减轻高脂和STZ诱导的2型糖尿病大鼠肝脏中的氧化应激，有效地使肝脏葡萄糖代谢和胰岛素信号正常化。
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