INHIBITION OF NA CA EXCHANGE STIMULATES INSULIN RELEASE FROM ISOLATEDRAT PANCREATIC-ISLETS/

Na/Ca exchange was recently shown to regulate cytosolic free Ca2+ conc entration ([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 Ca-45 outflow but did not incre ase insulin release from islets perifused in the presence of 2.8 mM gl ucose. By contrast, in the absence of extracellular Na+, caffeine almo st failed to increase Ca-45 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 islet s perifused at a higher glucose concentration (8.3 mM) except that, in the presence of extracellular Na+, caffeine more markedly increased C a-45 outflow and stimulated insulin release. Our data provide direct e vidence that inhibition of Na/Ca exchange with resulting blockade of C a2+ outflow may increase insulin release from the pancreatic B-cell un der suitable experimental conditions.