Objective To investigate the effect of ferulic acid,a natural compound,on pancreatic beta cell viability,Ca^(2+)channels,and insulin secretion.Methods We studied the effects of ferulic acid on rat insulinoma cell line...Objective To investigate the effect of ferulic acid,a natural compound,on pancreatic beta cell viability,Ca^(2+)channels,and insulin secretion.Methods We studied the effects of ferulic acid on rat insulinoma cell line viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay.The whole-cell patch-clamp technique and enzyme-linked immunosorbent assay were also used to examine the action of ferulic acid on Ca^(2+)channels and insulin secretion,respectively.Results Ferulic acid did not affect cell viability during exposures up to 72 h.The electrophysiological study demonstrated that ferulic acid rapidly and concentration-dependently increased L-type Ca^(2+)channel current,shifting its activation curve in the hyperpolarizing direction with a decreased slope factor,while the voltage dependence of inactivation was not affected.On the other hand,ferulic acid have no effect on T-type Ca^(2+)channels.Furthermore,ferulic acid significantly increased insulin secretion,an effect inhibited by nifedipine and Ca^(2+)-free extracellular fluid,confirming that ferulic acid-induced insulin secretion in these cells was mediated by augmenting Ca^(2+)influx through L-type Ca^(2+)channel.Our data also suggest that this may be a direct,nongenomic action.Conclusion This is the first electrophysiological demonstration that acute ferulic acid treatment could increase L-type Ca^(2+)channel current in pancreaticβcells by enhancing its voltage dependence of activation,leading to insulin secretion.展开更多
基金This research project was supported by Mahidol University,Thailand.We also thank the Faculty of Medicine Siriraj Hospital,Mahidol University,for additional financial support to K.R.and W.B.W。
文摘Objective To investigate the effect of ferulic acid,a natural compound,on pancreatic beta cell viability,Ca^(2+)channels,and insulin secretion.Methods We studied the effects of ferulic acid on rat insulinoma cell line viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay.The whole-cell patch-clamp technique and enzyme-linked immunosorbent assay were also used to examine the action of ferulic acid on Ca^(2+)channels and insulin secretion,respectively.Results Ferulic acid did not affect cell viability during exposures up to 72 h.The electrophysiological study demonstrated that ferulic acid rapidly and concentration-dependently increased L-type Ca^(2+)channel current,shifting its activation curve in the hyperpolarizing direction with a decreased slope factor,while the voltage dependence of inactivation was not affected.On the other hand,ferulic acid have no effect on T-type Ca^(2+)channels.Furthermore,ferulic acid significantly increased insulin secretion,an effect inhibited by nifedipine and Ca^(2+)-free extracellular fluid,confirming that ferulic acid-induced insulin secretion in these cells was mediated by augmenting Ca^(2+)influx through L-type Ca^(2+)channel.Our data also suggest that this may be a direct,nongenomic action.Conclusion This is the first electrophysiological demonstration that acute ferulic acid treatment could increase L-type Ca^(2+)channel current in pancreaticβcells by enhancing its voltage dependence of activation,leading to insulin secretion.
