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.
Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.
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Adisakwattana
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Hsu
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Yibchok-anun
D000818:Animals; D001120:Arginine / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000737:chemistry; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D002934:Cinnamates / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D054086:KATP Channels / Q000037:antagonists & inhibitors; D007700:Kinetics; D008297:Male; D049990:Membrane Transport Modulators / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D055571:Secretory Pathway / Q000187:drug effects
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002934:Cinnamates; D007004:Hypoglycemic Agents; D007328:Insulin; D054086:KATP Channels; D049990:Membrane Transport Modulators; C063318:4-methoxycinnamic acid; D001120:Arginine; D005947:Glucose