FATE OF H-3-LABELED AND C-14-LABELED A-4166 IN PANCREATIC-ISLETS

The fate of H-3- and C-14-labelled A-4166 was examined in rat pancreat ic islets, The net uptake of the meglitinide analogue by islets incuba ted for 60 min in the presence of 0.1 mM A-4166 and then submitted to repeated washes was close to 0.1 pmol/islet. It was significantly incr eased when the concentration of D-glutose in the incubation medium was raised from 2.8 to 16.7 mM. No sizeable internalization of tritiated A-4166 into insulin-producing cells could be detected by autoradiograp hy. These findings suggest that the interaction of A-4166 with the bet a-cell may be restricted to its insertion on the plasma membrane and b inding to sulphonylurea receptors.