Mechanisms of p-methoxycinnamic acid-induced increase in insulin secretion

p-Methoxycinnamic acid (p-MCA) is a cinnamic acid derivative that shows various pharmacologic actions such as hepatoprotective and antihyperglycemic activities. The present study was to elucidate the mechanisms by which p-MCA increases Ca2?]i and insulin secretion in INS-1 cells. p-MCA (100 μM) increased Ca2?]i in INS-1 cells. The p-MCA-induced insulin secretion and rise in Ca2?]i were markedly inhibited in the absence of extracellular Ca2? or in the presence of an L-type Ca2? channel blocker nimodipine. These results suggested that p-MCA increased Ca2? influx via the L-type Ca2? channels. Diazoxide, an ATP-sensitive K? channel opener, did not alter p-MCA-induced insulin secretion, nor Ca2?]i response. In addition, p-MCA enhanced glucose-, glibenclamide-induced insulin secretion whereas it also potentiated the increase in insulin secretion induced by arginine, and Bay K 8644, an L-type Ca2? channel agonist. Taken together, our results suggest that p-MCA stimulated insulin secretion from pancreatic β-cells by increasing Ca2? influx via the L-type Ca2? channels, but not through the closure of ATP-sensitive K? channels.