木棉皮通过抑制PTP1B改善糖尿病小鼠的糖代谢

Mumianpi(Bombax malabaricum DC.Cortex)Improves Glucose Metabolism by Inhibiting PTP1B in Diabetic Mice

目的探讨木棉皮醇提物对糖尿病小鼠降血糖作用及抑制蛋白酪氨酸磷酸酯酶1B(PTP1B)治疗糖尿病的机制。方法采用腹腔注射链脲佐菌素(STZ)建立糖尿病小鼠模型,将其随机分为模型组,二甲双胍组和木棉皮高、中、低剂量组,进行5周灌胃给药。观察给药第7天、第14天、第21天、第28天、第35天小鼠的空腹血糖。给药结束后,检测口服葡萄糖耐量及葡萄糖刺激胰岛素释放能力;苏木精-伊红(HE)染色观察小鼠胰腺组织形态;Western bolt法测定PTP1B、胰岛素受体底物-1(IRS-1)、磷酸化胰岛素受体底物-1(pIRS-1)、蛋白激酶B(Akt)、磷酸化蛋白激酶B(pAKT)蛋白表达情况。结果木棉皮醇提取物可显著降低糖尿病小鼠的空腹血糖(P<0.001)并改善糖耐量(P<0.05),增强糖尿病小鼠的葡萄糖刺激胰岛素释放能力(P<0.05),减轻胰岛损伤;木棉皮醇提取物能够减少PTP1B蛋白的表达(P<0.05),同时显著提高pIRS-1/IRS-1蛋白比例、pAkt/Akt蛋白比例(P<0.05)。结论木棉皮醇提取物可降低糖尿病小鼠的血糖,可能是通过抑制PTP1B的表达,改善PI3K/Akt信号通路介导的胰岛素信号转导,进而促进血糖代谢。

Objective To observe the hypoglycemic effect of alcoholic extract of Mumianpi(Bombax malabaricum DC.cortex)and the protein tyrosine phosphatase 1(BPTP1B)inhibiting mechanism in typeⅡdiabetic mice.Methods The diabetic mice model was established using intraperitoneal injection of streptozotocin.The mice were randomly divided into model,metformin and Mumianpi(Bombax malabaricum DC.cortex)high,medium and low dose groups.All mice received 5-week drug treatment by gavage.The fasting blood glucose levels on day 7,14,21,28 and 35 of administration were tested.At the end of administration,oral glucose tolerance and glucose-stimulated insulin release capacity were determined.Histomorphology of mice pancreas was observed by HE staining.The levels of PTP1B,IRS-1,pIRS-1,Akt and pAkt protein in liver were measured by Western bolt method.Results The ethanolic extract of Mumianpi(Bombax malabaricum DC.cortex)significantly reduced the fasting blood glucose(P<0.05)and improved glucose tolerance(P<0.05),as well as enhanced glucose-stimulated insulin release capacity(P<0.05)and alleviated islet damage in diabetic mice.The ethanolic extract reduced the level of PTP1B protein(P<0.05),while significantly increased the ratio of pIRS-1/IRS-1 protein and pAkt/Akt protein(P<0.05).Conclusion The ethanolic extract of Mumianpi(Bombax malabaricum DC.cortex)reduced blood glucose in diabetic mice,which probably mediated by inhibiting the level of PTP1B and improving PI3K/Akt mediated insulin signal transduction.