Article date: November 1980
By: P. DONATSCH, D.A. LOWE, B.P. RICHARDSON, PAMELA TAYLOR in Volume 70, Issue 3, pages 355-362
Isolated islets of Langerhans from the rat have been used in studies designed to elucidate the mechanism by which cyproheptadine inhibits insulin secretion.
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.
Cyproheptadine completely inhibited Ca2+ uptake induced by d‐glucose and high K+o, two agents which depolarize the islet β‐cell membrane, whilst Ca2+ uptake elicited by removal of extracellular Na+ (i.e. Na+‐Ca2+ counter transport) was only slightly reduced.
A significant increase in Na+ uptake produced by veratridine was sensitive to tetrodoxin but only partially reduced by cyproheptadine.
These results suggest that cyproheptadine inhibits depolarization‐dependent calcium entry into pancreatic β‐cells.
Isolated islets of Langerhans from the rat have been used in studies designed to elucidate the mechanism by which cyproheptadine inhibits insulin secretion.
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.
Cyproheptadine completely inhibited Ca2+ uptake induced by d‐glucose and high K+o, two agents which depolarize the islet β‐cell membrane, whilst Ca2+ uptake elicited by removal of extracellular Na+ (i.e. Na+‐Ca2+ counter transport) was only slightly reduced.
A significant increase in Na+ uptake produced by veratridine was sensitive to tetrodoxin but only partially reduced by cyproheptadine.
These results suggest that cyproheptadine inhibits depolarization‐dependent calcium entry into pancreatic β‐cells.
DOI: 10.1111/j.1476-5381.1980.tb08710.x
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