The present study examines the acute effect of leptin (50 nM) on insulin secretion and on the fractional outflow rates of Ca-45(2+) and Rb-86(+) from pancreatic islets isolated from male lean albino rats. Under a constant physiological glucose concentration (5.6 mM), the addition of leptin to the perifusion medium led to an increment in Ca-45(2+) fractional outflow rate followed by a significant (p < 0.05) increase (26%) in the insulin release. At low glucose concentration (2.8 mM), leptin also elicited a significant (p < 0.05; 50-60%) increase in insulin secretion. However, under supraphysiological (16.7 mM) glucose concentration, the rapid first-phase insulin secretion response was abolished. At low glucose levels, islets perifused in the presence of leptin presented a lower Rb-86(+) fractional outflow rate compared with perifused controls. In contrast, when glucose was switched to 16.7 mM, compared with controls, a slight increase in the Rb-86(+) fractional outflow rate was observed instead. These in vitro data provide evidence that, by changing Kf fluxes, leptin might modulate insulin secretion from pancreatic islets. (C) 1999 Elsevier Science Inc. All rights reserved.