Mechanism by which cyproheptadine inhibits insulin secretion.
1 Isolated islets of Langerhans from the rat have been used in studies designed to elucidate the mechanism by which cyproheptadine inhibits insulin secretion. 2 D-Glucose and tolbutamide, both of which require extracellular Ca2+ to produce insulin release, failed to evoke a secretory response from islets pretreated with cyproheptadine. Conversely veratridine, the calcium ionophore A23187 and theophylline, all of which are capable of mobilizing sufficient intracellular Ca2+ to evoke insulin secretion in the absence of extracellular Ca2+, produced similar responses from cyproheptadine pretreated and control islets. 3 Cyproheptadine completely inhibited Ca2+ uptake induced by D-glucose and high Ko+, two agents which depolarize the islet beta-cell membrane, whilst Ca2+ uptake elicited by removal of extracellular Na+ (i.e. Na+-Ca2+ counter transport) was only slightly reduced. 4 A significant increase in Na+ uptake produced by veratridine was sensitive to tetrodoxin but only partially reduced by cyproheptadine. 5 These results suggest that cyproheptadine inhibits depolarization-dependent calcium entry into pancreatic beta-cells.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003533:Cyproheptadine / Q000494:pharmacology*; D003864:Depression, Chemical; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology; D013997:Time Factors; D014044:Tolbutamide / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D007328:Insulin; D003533:Cyproheptadine; D014701:Veratridine; D014044:Tolbutamide; D012964:Sodium; D013806:Theophylline; D002118:Calcium