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. 1989 Nov;98(3):875–882. doi: 10.1111/j.1476-5381.1989.tb14616.x

Effects of extracellular adenine nucleotides on the electrical, ionic and secretory events in mouse pancreatic beta-cells.

P Petit 1, G Bertrand 1, W Schmeer 1, J C Henquin 1
PMCID: PMC1854764  PMID: 2686791

Abstract

1. The mechanisms whereby extracellular adenine nucleotides modulate pancreatic beta-cell function were studied with mouse islets stimulated by 15 mM glucose. 2. Adenosine 5'-triphosphate (ATP) and adenosine 5'-diphosphate (ADP) (100 microM) inhibited insulin release, 45Ca efflux and 86Rb efflux from islet cells, and decreased electrical activity in beta-cells. These changes were rapid but small and transient. 3. alpha,beta-Methylene ADP caused a rapid and sustained inhibition of insulin release, 45Ca efflux and 86Rb efflux from islet cells. It also produced a slight hyperpolarization of the beta-cell membrane, with sustained modification of the pattern but only transient decrease of the intensity of the electrical activity. In the absence of extracellular Ca2+, alpha,beta-methylene ADP increased 45Ca and 86Rb efflux without changing insulin release. Most effects of alpha,beta-methylene ATP were qualitatively similar but quantitatively smaller than those of the ADP-analogue. 4. Adenylylimido-diphosphate (AMP-PNP) slightly increased 45Ca and 86Rb efflux and potentiated insulin release in the presence of extracellular Ca2+. However, its effects on electrical activity in beta-cells were qualitatively similar to those of the alpha,beta-methylene analogues. 5. The small effects of ATP and ADP could result from their degradation into adenosine. alpha,beta-Methylene ADP appears to increase K+ permeability of the beta-cell membrane and to produce a second, intracellular, effect which largely contributes to the inhibition of insulin release. Another recognition site, with higher affinity for triphosphate derivatives, could mediate the small stimulatory effects of AMP-PNP.

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Selected References

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