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

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.