桑酮碱对2型糖尿病db/db小鼠血糖及肝脏胰岛素抵抗的影响

摘要

AIM To explore the effects of Sangtong alkaloids (total alkaloids and total flavones from Mori folium,STA) on the random blood glucose,starch tolerance and hepatic insulin resistance in db/db mice with type 2 diabetes mellitus.METHODS Eight-week-old db/db mice were divided into model group (normal saline),acarbose group (39 mg/kg) and Sangtong alkaloids groups (105,210 and 420 mg/kg),db/m mice were used as control group (normal saline).The mice were given by intragastric administration for one hundred days.The random blood glucose of mice was determined every ten days.The starch tolerance was determined in the 100th day,together with the determination of serum insulin level,insulin resistance index and insulin sensitivity index.Histopathology changes of pancreas were observed by HE staining.Protein expressions of P-IRS1,P-PI3 K,P-AKT and GLUT2 were detected by Western blot.RESULTS Sangtong alkaloids significantly decreased the random blood glucose,serum insulin level and insulin resistance index,and increased the insulin sensitivity index in db/db mice.Meanwhile,Sangtong alkaloids ameliorated the pancreas histopathological damage and up-regulated the protein expressions of P-IRS1,P-PI3K,P-AKT and GLUT2 in liver.CONCLUSION Sangtong alkaloids can decrease the random blood glucose and improve the insulin resistance of liver in db/db mice with type 2 diabetes mellitus,whose mechanism may be associated with the regulation of hepatic insulin signal pathway.%目的 探讨桑酮碱(桑叶总黄酮和总生物碱,STA)对2型糖尿病db/db小鼠随机血糖、淀粉耐量、肝脏胰岛素抵抗的影响.方法 8周龄db/db小鼠分为模型组(生理盐水)、阿卡波糖组(39 mg/kg)、桑酮碱组(105、210、420 mg/kg),db/m小鼠为空白组(生理盐水).小鼠灌胃给药100 d,每10 d测定小鼠随机血糖;第100天检测淀粉耐受情况;测定血清胰岛素水平、胰岛素抵抗指数、胰岛素敏感指数;HE染色观察胰腺组织病理学变化;Westernbolt法测定磷酸化胰岛素受体底物1(P-IRS1)、磷酸化磷酯酰肌醇-3激酶(P-PI3K)、磷酸化蛋白激酶B(P-AKT)、葡萄糖转运蛋白2 (GLUT2)蛋白表达.结果 桑酮碱能够显著降低db/db小鼠随机血糖、血清胰岛素水平、胰岛素抵抗指数,提高胰岛素敏感指数,改善胰腺组织病理形态损伤,上调肝脏P-IRS1、P-PI3K、P-AKT、GLUT2蛋白表达.结论 桑酮碱具有降低2型糖尿病db/db小鼠随机血糖、改善肝脏胰岛素抵抗的作用,其机制可能与调节肝脏胰岛素信号通路有关.