醛固酮对3T3-L1脂肪细胞PTEN及p-Akt蛋白表达的影响

Effect of aldosterone on PTEN expression and the PI3K-Akt pathway in 3T3-L1 adipocytes

目的观察胰岛素抵抗(IR)的脂肪细胞中Aktser 473磷酸化(p-Akt)水平和与张力蛋白同源10号染色体缺失的磷酸酶基因(PTEN)蛋白的表达,以及醛固酮和螺内酯处理后上述蛋白表达的变化,从而探讨醛固酮在IR发病机制中的作用。方法通过地塞米松与胰岛素共同诱导3T3-L1前脂肪细胞建立IR模型,western blots方法检测正常分化及IR的脂肪细胞PTEN蛋白和p-Akt水平,观察醛固酮和螺内酯对细胞PTEN蛋白表达及p-Akt水平的影响。结果 IR脂肪细胞PTEN的蛋白水平较正常分化脂肪细胞显著升高[(0.83±0.11)vs(0.63±0.06),P<0.05],高浓度醛固酮可增加PTEN蛋白表达,经螺内酯处理后PTEN蛋白表达明显下调(P均<0.05);IR脂肪细胞模型p-Akt水平明显低于正常分化脂肪细胞[(0.52±0.12)vs(0.78±0.12),P<0.05],高浓度醛固酮可下调p-Akt水平,螺内酯可部分逆转醛固酮的抑制作用(P均<0.05)。结论醛固酮可能通过PI3K-AKT通路导致IR的发生。

Objective To investigate the effects of aldosterone on the expression of phosphoserine 473-Akt and PTEN in normal or insulin resistant adipocytes,with the aim to explore the role of aldosterone in the pathogenesis of insulin resistance.Methods Insulin resistant 3T3-L1 adipocytes were induced by dexamethasone and insulin.The protein expressions of PTEN and phosphoserine 473-AKT in normal and insulin resistant adipocytes treated with aldosterone or spironolactone were measured by Western blot.Results Compared with normal adipocytes,expression of PTEN protein increased（0.83±0.11） vs（0.63±0.06） ,P0.05]and phosphoserine 473-AKT protein decreased（0.52±0.12） vs（0.78±0.12） ,P0.05]in insulin resistant models.Aldosterone-induced up-regulation of PTEN and degradation of phosphoserine 473-AKT was markedly attenuated by spironolactone,a mineralocorticoid receptor antagonist（all P0.05） .Conclusion Aldosterone induces insulin resistance possibly via the PI3K-Akt pathway in 3T3-L1 adipocytes.