大黄素对糖尿病KKAy小鼠PI3-K信号转导通路的影响

Effects of emodin on KKAy diabetic mouse in PI3-K signal transduction pathway

目的观察大黄素对2型糖尿病模型KKAy小鼠血糖、胰岛素水平及磷脂酰肌醇3-激酶(PI3-K)信号转导通路的影响。方法随机血糖均≥13.9 mmol/L的SPF级KKAy小鼠16只,随机分为模型组和治疗组各8只,另选8只C57BL/6J小鼠为正常组。正常组和模型组灌服20 mL/(d.kg)无菌水,治疗组予50 mg/kg大黄素灌胃。8周后测定各组小鼠空腹血糖(FPG)、空腹胰岛素(FINS)并计算胰岛素敏感指数(ISI);用Western blot法测定三组小鼠骨骼肌、脂肪组织中胰岛素受体底物-1(IRS-1)、PI3-K水平及Akt丝氨酸(Ser)473磷酸化水平。结果模型组小鼠较正常组FPG、FINS明显升高,ISI明显降低,而治疗组小鼠的FPG、FINS较模型组明显降低,ISI明显升高(P均<0.05)。模型组IRS-1、PI3-K表达水平及胰岛素刺激后Akt Ser473磷酸化升高倍数低于正常组,治疗组IRS-1、PI3-K表达水平及Akt Ser473磷酸化升高倍数高于模型组(P均<0.05)。结论大黄素灌胃可降低2型糖尿病模型KKAy小鼠血糖、胰岛素水平,并增强胰岛素敏感度,提高小鼠骨骼肌及脂肪组织中的IRS-1、PI3-K水平及Akt Ser473磷酸化水平。

Objective To observe the effects of emodin in type 2 diabetic KKAy mice blood glucose,insulin levels and phosphatidylinositol 3-kinase（PI3-K） signal transduction pathway.Methods 16 specific pathogen free（SPF） KKAy mice were divided randomly according to plasma glucose level into model group and treatment group,8 normal C57BL/6J mice were selected as normal group.Mice of normal group and model group were fed with 20 mL/（d · kg） of sterile water,treatment group were given 50 mg/kg emodin orally.8 weeks later,all animals were tested fasting plasma glucose（FPG）,fasting insulin level for caculating insulin sensitivity index（ISI）,total triacylglycerol（TG）,total cholesterol（TC）.The expression of IRS-1,PI3-K and Akt Ser473 in the musle tissue and adipose tissue were determined by Western blot.Results Compared with normal group,model group showed higher FBG,TG and TC,lower ISI（all P0.05）,and lower expression of IRS-1,PI3-K and Akt Ser473 in the musle tissue and adipose tissue（all P0.05）.Compared with model group,treatment group showed lower FBG,TG and TC higher ISI（all P0.05）.The expression of IRS-1,PI3-K and Akt Ser473 in the musle tissue and adipose tissue of treatment group is up-regulated as compared with model group（all P0.05）.Conclusion Emodin can increase the expression of IRS-1,PI3-K and Akt Ser473 in the musle tissue and adipose tissue,decrease FBG and improves insulin sensitivity of KKAy diabetic mice.