Abstract
Activation of α 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.
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Debuyser, A., Drews, G. & Henquin, J.C. Adrenaline inhibition of insulin release: role of the repolarization of the B cell membrane. Pflügers Arch. 419, 131–137 (1991). https://doi.org/10.1007/BF00372998
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DOI: https://doi.org/10.1007/BF00372998