Membrane and intracellular effects of adenosine in mouse pancreatic beta-cells

Mouse islets were used to study the effects of adenosine and its stable analogue L-N6-phenylisopropyladenosine (L-PIA) on pancreatic beta-cell function. At a high concentration (500 microM), adenosine augmented glucose-induced electrical activity in beta-cells and potentiated insulin release. These effects were prevented by the inhibitor of nucleoside transport nitrobenzylthioguanosine. They probably result from the metabolism of adenosine by beta-cells. At a lower concentration (50 microM), adenosine caused a small and transient inhibition of glucose-induced electrical activity and insulin release. L-PIA (10 microM) slightly and transiently inhibited insulin release, 45Ca efflux and 86Rb efflux from islet cells, and decreased electrical activity in beta-cells. When adenylate cyclase was stimulated by forskolin in the presence of 15 mM glucose, insulin release was strongly augmented. Under these conditions, L-PIA and adenosine (with nitrobenzylthioguanosine) caused a sustained inhibition. No such inhibition was observed when insulin release was potentiated by dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP). These data are consistent with the existence of A1 purinergic receptors on mouse beta-cells. They could mainly serve to attenuate the amplification of insulin release brought about by agents acting via cAMP.