Regulation of calcium fluxes in rat pancreatic islets: calcium extrusion by sodium-calcium countertransport.
The mechanisms by which glucose regulates calcium fluxes in pancreatic endocrine cells were investigated by monitoring the efflux of 45Ca from prelabeled and perifused rat pancreatic islets. In the absence of both extracellular calcium and glucose, partial or total removal of extracellular sodium decreases the efflux of 45Ca from prelabeled islets. Glucose also reduces the efflux of 45Ca from islets perifused in the absence of extracellular calcium. This inhibitory effect of glucose on 45Ca efflux is decreased by half when the extracellular concentration of sodium is lowered to 24 mM. In the absence of extracellular calcium but presence of glucose, partial or even total removal of extracellular sodium fails to decrease the efflux of 45Ca. At normal extracellular calcium concentration (1 mM) partial removal of extracellular sodium dramatically increases 45Ca efflux from pancreatic islets. This increase in 45Ca efflux is partially but not totally suppressed by either 16.7 mM glucose or cobalt. It is totally suppressed by 4.4 mM glucose or by the combination of 16.7 mM glucose and cobalt. At normal extracellular calcium concentration, glucose initially reduces and subsequently increases 45Ca efflux. The initial fall is unaffected by tetrodotoxin but decreased by 50% at low extracellular sodium concentration (24 mM). The present results suggest the existence in pancreatic endocrine cells of a glucose-sensitive process of sodium-calcium counter-transport. By inhibiting such a process, glucose may decrease the efflux of calcium from islet cells. The effect of glucose is not mediated by an increase in intracellular sodium concentration. It could contribute to the intracellular accumulation of calcium which is thought to trigger insulin release.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D003035:Cobalt / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D007328:Insulin; D003035:Cobalt; D013779:Tetrodotoxin; D012964:Sodium; D005947:Glucose; D002118:Calcium