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.
Bertrand
G
G
Unité de Diabétologie et Nutrition, University of Louvain Faculty of Medicine, Brussels, Belgium.
Petit
P
P
Bozem
M
M
Henquin
J C
JC
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006151:Guanosine / Q000494:pharmacology / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D013872:Thionucleosides / Q000494:pharmacology
D007328:Insulin; D013872:Thionucleosides; D006151:Guanosine; C002121:6-(4-nitrobenzylthio)guanosine; D005576:Colforsin; D010660:Phenylisopropyladenosine; D005947:Glucose; D000241:Adenosine