Inhibition of Na/Ca exchange stimulates insulin release from isolated rat pancreatic islets.
Na/Ca exchange was recently shown to regulate cytosolic free Ca2+ concentration ([Ca2+]i) in the pancreatic B-cell. The aim of the present study was to provide direct evidence that inhibition of the activity of the exchange may also increase insulin release. In the presence of extracellular Na+, caffeine stimulated 45Ca outflow but did not increase insulin release from islets perifused in the presence of 2.8 mM glucose. By contrast, in the absence of extracellular Na+, caffeine almost failed to increase 45Ca outflow and reversibly stimulated insulin release despite the fact that the absence of extracellular Na+ per se reduced basal insulin release. Similar findings were observed in islets perifused at a higher glucose concentration (8.3 mM) except that, in the presence of extracellular Na+, caffeine more markedly increased 45Ca outflow and stimulated insulin release. Our data provide direct evidence that inhibition of Na/Ca exchange with resulting blockade of Ca2+ outflow may increase insulin release from the pancreatic B-cell under suitable experimental conditions.
van Eylen
F
F
Laboratory of Pharmacology, Brussels Free University, School of Medicine, Belgium.
Antoine
M H
MH
Lebrun
P
P
Herchuelz
A
A
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D007328:Insulin; D019831:Sodium-Calcium Exchanger; D002110:Caffeine; D012964:Sodium; D002118:Calcium