Effect of the meglitinide analog S21403 on cationic fluxes and insulin release in perifused rat pancreatic islets exposed to a high concentration of D-glucose

The effect of the meglitinide analog S21403 (10 mu M) upon Rb-86 and Ca-45 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 Rb-86 outflow, Ca-45 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. (C) 1999 Academic Press.