Study On The Effect Of Insulin And Glucose Regulate Acyl CoenzymeA: Cholesterol Acyltransferase-1 And The Mechanism Of Transduction Signaling

Partâ… Influence of insulin and glucose on acyl coenzymeA:cholesterol acyltransferase-1 expression of THP-1 derived macrophagesObjective To investigate the effects of insulin and glucose on acyl coenzymeA: cholesteryl acyltransferase 1(ACAT-1) expression in THP-1-derived macrophages.Method THP-1 cells were incubated with PMA for 48 hours then exposed to various concentration of glucose and/or insulin for 12 hours. The ACAT-1 mRNA level of cells was determined by Real-time PCR. The protein of ACAT-1 was detected by Western blot.Results High concentration of glucose increased the expression of ACAT-1 mRNA and protein secretion compared to that of the control group ( P <0. 01). In contrast , there were no significant differences between low glucose group and control group ( P > 0.05). Under different concentrations of glucose, stimulation of ACAT-1 levels by insulin was sufficient to increased. Low glucose and insuline group significantly affect ACAT-1 activity versus high glucose without insulin ( P <0. 01). And high glucose and insuline group upregulate ACAT-1 activity versus low glucose and insulin group ( P <0. 01). In addition, insulin and glucose administration to macrophages enhanced both mRNA expression and protein secretion of ACAT-1 in a time-dose-dependent manner. Conclusion Glucose and insulin up-regulate ACAT-1 expression in THP-1-derived macrophages, which maybe involved in the pathological progress of atherosclerosis in metabolic syndrome.Partâ…¡The signaling pathway of glucose and insulin on acyl coenzymeA:cholesterol acyltransferase-1 expression of THP-1 derived macrophagesObjective To study the signaling pathway of glucose and insulin on acyl coenzymeA: cholesterol acyltransferase-1(ACAT-1) expression of THP-1 derived macrophages. Methods THP-1 cells were incubated with PMA for 48 hours. After pretreated with two protein kinase inhibitors for 1h: ERK activity inhibitor PD98059(PD), PI3K activity inhibitor Wortamanin(WT), cells were stimulated with insulin and glucose for 12h. The ACAT-1 mRNA level of cells was determined by RealTime-PCR. The content of ACAT-1 protein was detected by Westernblot.Results PD suppress the expression of ACAT-1 mRNA and protein secretion compared to that of the insulin and glucose group ( P <0. 01). In contrast , there were no significant differences between PD group and control group (P > 0.01). However WT group has the same expression of ACAT-1 mRNA and protein secretion compared to that of the insulin and glucose group ( P >0. 01). In contrast , there were significant differences between PD group and control group ( P< 0.01).Conclusion ERK plays an important role in the biosynthesis of ACAT-1 mRNA and protein induced by insulin and glucose in THP-1 macrophages, while WT may have no significant role.