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地塞米松与胰岛素合用促进去甲肾上腺素合成及其释放机制研究

Mechanism of increasing synthesis and secretion of norepinephrine induced by combined insulin and dexamethasone

  • 摘要: 胰岛素和地塞米松近来被证实可能在胰岛素抵抗过程中与交感神经系统兴奋有关。将以PC12细胞为研究对象,探讨地塞米松与胰岛素及两者合用对于PC12细胞去甲肾上腺素合成及释放的影响及其机制。在给予相应药物孵育24 h后,使用荧光分光光度计检测胞内游离钙离子和去甲肾上腺素含量等指标变化。胰岛素与地塞米松共同作用时,PC12细胞合成及释放的NE较两者单用有显著性上升,胞内多巴胺含量较单用胰岛素时有明显下降;α-甲基-对位酪氨酸和米非司酮可明显拮抗地塞米松在此过程中的作用;尼莫地平和肝素可分别明显阻断胰岛素和地塞米松对胞内游离钙离子的影响。结果表明:地塞米松可以与胰岛素分别通过电压门控型钙通道的IP3受体两种不同途径进一步增加PC12细胞内游离钙离子,并通过酪氨酸羟化酶、多巴胺β-羟化酶和糖皮质激素核受体途径来促进去甲肾上腺素合成及释放。

     

    Abstract: Several reports suggested that insulin and dexamethasone may induce the excitation of sympathetic nervous system during insulin resistance.In order to explore the effects and the mechanism on the cellular synthesis and secretion of norepinephrine (NE) of co-incubated insulin and dexamethasone,the concentrations of free Ca2+ and NE in PC12 cells after 24 h co-incubation with appropriate agents were detected by fluorescence spectrophotometer.It was found that co-incubation with insulin and dexamethasone increased significantly both synthesis and secretion of NE in PC12 cells when compared to the presence of insulin only.However,the synthesis of dopamine decreased significantly. This tendency was attenuated by α-methyl-tyrosine(α-MT)and mifepristone.Furthermore,nimodipine or heparin impeded the enhancement in free Ca2+ concentration of PC12 cells induced separately by insulin and dexamethasone.In conclusion,combination of dexamethasone and insulin may increase the concentration of free Ca2+ in PC12 cells independently by activating voltage-gated calcium channel and IP3 receptor,and finally facilitates the synthesis and secretion of NE in PC12 cells via tyrosine hydroxylase,dopamine β-hydroxylase and glucocorticoid nuclear receptor.

     

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