Abstract
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.
Key words
p-methoxycinnamic acid - diabetes - insulin secretion - INS-1 cells - Ca
2+ influx