Adrenaline inhibition of insulin release: role of the repolarization of the B cell membrane.
Activation of alpha 2-adrenergic receptors affects several signalling pathways in pancreatic B cells. However, since adrenaline can inhibit insulin release by interfering with a late step of the secretory process, the functional significance of the earlier effects is unclear. In this study, normal mouse islets were used to determine whether the repolarization of the B cell membrane caused by adrenaline contributes to the inhibition of insulin release. The decrease in 86Rb efflux and the repolarization of the B cell membrane produced by adrenaline were attenuated by tolbutamide, which depolarizes by blocking ATP-sensitive K+ channels, and by arginine, which depolarizes because of its transport in a charged form. It is also known that adrenaline does not affect the membrane potential and 86Rb efflux in B cells depolarized by high K+. These three depolarizing conditions similarly shifted to the right the concentration dependence of adrenaline inhibition of insulin release: the effect of 1 nM and 10 nM adrenaline was reduced, but high concentrations of adrenaline still inhibited insulin release nearly completely under all conditions. In contrast, increasing insulin release by cytochalasin B did not alter the inhibitory potency of adrenaline. It is concluded that the repolarization of the B cell membrane and the ensuing decrease in Ca2+ influx play a significant role in the inhibition of insulin release by low concentrations of adrenaline. When high concentrations are used, a more distal effect becomes predominant.
Debuyser
A
A
Unité de Diabétologie et Nutrition, University of Louvain, Faculty of Medicine, Brussels, Belgium.
Drews
G
G
Henquin
J C
JC
D000818:Animals; D001120:Arginine / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008564:Membrane Potentials; D051379:Mice; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
D007328:Insulin; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D001120:Arginine; D014044:Tolbutamide; D005947:Glucose; D004837:Epinephrine