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 [Ca(2+)](i) and insulin secretion in INS-1 cells. p-MCA (100 mu M) increased [Ca(2+)](i) in INS-1 cells. The p-MCA-induced insulin secretion and rise in [Ca(2+)](i) were markedly inhibited in the absence of extracellular Ca(2+) or in the presence of an L-type Ca(2+) channel blocker nimodipine. These results suggested that p-MCA increased Ca(2+) influx via the L-type Ca(2+) channels. Diazoxide, an ATP-sensitive K(+) channel opener, did not alter p-MCA-induced insulin secretion, nor [Ca(2+)](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 Ca(2+) channel agonist. Taken together, our results suggest that p-MCA stimulated insulin secretion from pancreatic beta-cells by increasing Ca(2+) influx via the L-type Ca(2+) channels, but not through the closure of ATP-sensitive K(+) channels.