Apelin对葡萄糖的毒性作用及对胰岛细胞PDX-1表达的影响

Effects of Apelin on glucose toxicity and islet cells PDX-1 expression

目的探讨Apelin对葡萄糖毒性作用及对胰岛细胞胰十二指肠同源盒蛋白-1(PDX-1)表达的影响。方法在不同葡萄糖浓度下(正糖组5.6mmol/L,高糖组16.7mmol/L,极高糖组33.3mmol/L),+/-Apelin-36培养胰岛β细胞株NIT-1细胞3d,然后测定基础和葡萄糖刺激后胰岛细胞胰岛素分泌量,测定细胞内胰岛素含量和PDX-1蛋白及mRNA表达。结果与正糖组比较,高糖组和极高糖组的基础和葡萄糖刺激后胰岛素分泌、细胞内胰岛素均明显减少,PDX-1蛋白表达下降(P<0.05);与未加Apelin组比较,加Apelin高糖组和极高糖组的基础和葡萄糖刺激后胰岛素分泌、细胞内胰岛素明显减少,PDX-1蛋白表达下降(P<0.05);6组胰岛细胞的胰岛素水平与PDX-1蛋白表达呈正相关,与PDX-1mRNA表达无关。结论 Apelin可能通过降低PDX-1蛋白表达参与葡萄糖毒性作用,引起胰岛素分泌减少,从而在糖尿病的发病机制中发挥作用。

Objective To study the effects of Apelin on glucose toxicity and islet cells PDX-1protein expression.MethodsThe isletβcell line NIT-1cells were incubated in the medium containing different glucose concentrations（normal glucose concentration group 5.6mmol/L,high glucose concentration group 16.7mmol/L,extremely high glucose concentration group 33.3mmol/L）and ＋/- Apelin-36 respectively for 3d.Then the basic insulin secretion amount of islet cells and their secretion amount after glucose stimulation were detected.The intracellular insulin content and the PDX-1protein and mRNA expression were detected.Results Compared with the normal glucose group,the basic insulin secretion,secretion after stimulation and intracellular insulin in the high glucose group and extremely high glucose group were significantly decreased and PDX-1protein expression was declined（P〈0.05）;compared with non-adding Apelin group,the basic insulin secretion,secretion after stimulation and intracellular insulin in the adding Apelin high glucose group and extremely high glucose group were significantly decreased and PDX-1protein expression was decreased（P〈0.05）;the insulin level in islet cells of 6groups was positively correlated with PDX-1protein expression and had no correlation with PDX-1mRNA expression.Conclusion Apelin may participate in the glucose toxic effect by decreasing PDX-1protein expression,causes the decrease of insulin secretion,thus plays a role in the pathogenesis of diabetes.