The stimulation of insulin secretion by glucose requires metabolism of the sugar in the pancreatic b-cell and involves the generation of electrical activity that results from depolarization of the b-cell membrane. The mechanisms whereby glucose depolarizes the pancreatic b-cell are not completely understood. It is generally believed that depolarization results from closure of KATP channels. However, there is considerable and increasing evidence from a number of laboratories for at least one additional ionic mechanism, independently of KATP channels and based on Anionic fluxes. In 1978, Sehlin already showed that a glucose concentration increase stimulates chloride efflux from 36Cl- preloaded islets. More recently, an anion-selective channel has been identified which generates an inward current. The channel is activated by glucose and by hypotonic cell swelling. This channel therefore appears to be a Volume-Regulated Anion Channel (VRAC). It is suggested that activation of the VRAC by glucose is a complementary mechanism leading to depolarization of the plasma membrane and hence electrical activity. Recently, we have developed a new promissing approach, using D-[2,3-3H]-aspartate in order to evaluate the activity of VRAC in whole islets assays. We have first characterized the net uptake of D-[2,3-3H]-aspartate by islets. This process is found to be time-, concentration- and temperature-dependent, but is independent of glucose concentration. Secondly, we have checked that, in prelabeled, then perifused islets, hypoosmolar conditions induced a dramatic increase in D-[2,3-3H]-aspartate efflux, validating this tracer for measurements of VRAC activities in islets. Then, we have focused on the effects of increasing concentrations of D-glucose on tritiated aspartate efflux and we have shown that a rise in the hexose concentration induces the opening of VRAC. Speculations about the possible mechanisms whereby glucoses activate VRAC will finally be discussed.