KKAy小鼠聚合酶delta作用蛋白2缺乏导致血糖异常的研究

Lack of a novel protein Poldip2 leads to metabolic abnormalities of glucose in KKAy mice

目的通过对2型糖尿病模型鼠KKAy中注入聚合酶delta作用蛋白2(Poldip2)腺病毒,探讨其对于胰岛素信号通路和小鼠肝脏的糖代谢的调节作用。方法利用特殊的糖尿病模型鼠即KKAy小鼠,将其随机分为磷酸盐缓冲液组(PBS组)、绿色荧光蛋白组(GFP组)和Poldip2组;C57BL/6J为正常对照组。利用Western blot检测小鼠肝脏的Poldip2的表达以及胰岛素信号通路中蛋白的表达水平,同时采用RT-PCR检测磷酸烯醇式丙酮酸羧激酶(PEPCK)、葡萄糖-6-磷酸酶(G6Pase)的mRNA表达的水平。结果通过对胰岛素信号通路相关蛋白检测,Poldip2组可降低10号染色体缺失的磷酸酶及张力蛋白同源(PTEN)表达,从而激活蛋白激酶B(Akt)促进胰岛素通路的传递,进而降低G6Pase、PEPCK表达来调节血糖。结论 Poldip2改善2型糖尿病鼠的糖代谢的机制可能是通过升高Poldip2的表达,激活NADPH氧化酶4(NOX4)产生过氧化物(H2O2),抑制了PTEN从而激活Akt活性,改善了胰岛素信号通路及糖代谢的紊乱。

Objective To investigate a novel protein polymerase delta-interacting protein 2(Poldip2)in the insulin signaling pathway and regulation glucose metabolism in KKAy mice.Methods KKAy mice,a special diabetic mouse model,were randomly divided into phosphate buffered solution(PBS)group,green fluorescent protein(GFP)group andpolymerase delta-interacting protein 2(Poldip2)group.C57BL/6J was normal control group.Western blot was used to detect the expression of Poldip2 and the expression of protein in insulin signaling pathway.Meanwhile,the mRNA levels of PEPCK and G6Pase were detected by RT-PCR.Results Poldip2 could decrease the expression of PTEN,then activated activity of Akt to promote insulin signaling pathway via detecting the protein of insulin signaling pathway.Meanwhile,it was found that Poldip2 reduce the expression of G6Pase and PEPCK,thereby inhibited the gluconeogenesis.Conclusion Poldip2 can improve glucose metabolism in type 2 diabetic mice by increasing Poldip2 expression,activating NADPH oxidase 4(NOX4)to produce peroxide(H 2O 2),inhibiting PTEN and activating Akt activity,improving insulin signaling pathway and dsorders of glucose metabolism.