Résumé : The effect of the meglitinide analog S21403 (10 μM) upon 86Rb and 45Ca outflow and insulin release was investigated in perifused rat islets exposed to a high concentration of D-glucose (16.7 mM) in order to simulate the situation found in diabetic patients. Under these conditions, S21403 provoked a rapid, sustained and rapidly reversible increase in 86Rb outflow, 45Ca efflux and insulin release. These effects were suppressed or reversed when the experiments were conducted in the absence of extracellular Ca2+. They support the view that S21043 could be used as a novel insulinotropic tool in the treatment of non-insulin-dependent diabetes mellitus, the cationic and secretory responses to the drug displaying a favourable time course for prompt and not unduly prolonged activation of islet B-cells.