分泌性卷曲相关蛋白5表达上调对小鼠肝脏糖代谢的影响

Effects of Over-expression of Secreted Frizzled-related Protein 5(SFRP5) on Glucose Metabolism in Mouse Liver

分泌性卷曲相关蛋白5(secreted frizzled-related protein 5,SFRP5)是一种抗炎脂肪因子,它与糖尿病密切相关,具有抗糖尿病作用。将8周龄的C57BL/6J小鼠随机分为4组:普食-空载病毒组(SD+Ad-GFP组,n=10)、普食-SFRP5过表达病毒组(SD+Ad-SFRP5组,n=10)、高脂-空载病毒组(HFD+Ad-GFP组,n=10)、高脂-SFRP5过表达病毒组(HFD+Ad-SFRP5组,n=10),各组喂养13周后,利用定量PCR技术及Western-blot技术,分别检测小鼠肝脏糖异生关键酶磷酸烯醇式丙酮酸羧激酶(phosphoenolpyruvate carboxykinase,PEPCK)和葡萄糖-6-磷酸酶(glucose-6-phosphatase,G6Pase)mRNA及蛋白质水平的变化情况,以及肝脏经典胰岛素信号通路的改变。结果显示:高脂喂养组中,SFRP5表达上调可使肝脏糖异生指标PEPCK和G6Pase的mRNA及蛋白质相对表达水平均降低(P<0.05),而且SFRP5过表达可使肝脏经典胰岛素信号通路指标胰岛素受体(InsR)及蛋白激酶B(AKT)的磷酸化水平增高(P<0.05)。以上结果说明,C57BL/6J小鼠体内过表达SFRP5可能通过降低肝脏糖异生,增强胰岛素信号通路,从而改善机体胰岛素抵抗状态。

Secreted frizzled-related protein 5 （SFRP5） is one of anti-inflammatory lipid mediators, and is found to play regulatory roles in obesity-induced diabetes. Herein, four groups of eight-week-old C57BL/6J mice were randomly assigned as normal fat diet （SD）-empty adenovirus （Ad-GFP） （n=10）, normal fat diet （SD）-adenovirus over-expression SFRP5 （Ad-SFRP5） （n=10）, high fat diet （HFD）-empty adenovirus （Ad-GFP） （n=10）, and high fat diet （HFD）-adenovirus over-expression SFRP5 （Ad-SFRP5） （n=10）. After 12 weeks, phosphoenolpyruvate carboxykinase （PEPCK） and glucose-6-phosphatase （G6Pase） mRNA and protein expression in the mice livers were measured by real-time PCR and Western-blot, respectively. The phosphorylation of insulin signaling pathway was measured by Western-blot. The results showed that both mRNA and protein expression levels of PEPCK and G6Pase were significantly decreased （P〈0.05）, and the levels of phosphorylation of insulin receptors （InsR） and protein kinase B （AKT） were significantly increased in HFD-Ad-SFRP5 group （P〈0.05）. Thus, over-expression of SFRP5 in C57BL/6J mice may improve insulin resistance in the liver by decreasing hepatic gluconeogenesis and enhancing the insulin signaling pathway.