The mechanisms whereby extracellular adenine nucleotides modulate pancreatic β‐cell function were studied with mouse islets stimulated by 15 mm glucose.

Adenosine 5′‐triphosphate (ATP) and adenosine 5′‐diphosphate (ADP) (100 μm) inhibited insulin release, ⁴⁵Ca efflux and ⁸⁶Rb efflux from islet cells, and decreased electrical activity in β‐cells. These changes were rapid but small and transient.

α,β‐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 β‐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⁺, α,β‐methylene ADP increased ⁴⁵Ca and ⁸⁶Rb efflux without changing insulin release. Most effects of α,β‐methylene ATP were qualitatively similar but quantitatively smaller than those of the ADP‐analogue.

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 β‐cells were qualitatively similar to those of the α,β‐methylene analogues.

The small effects of ATP and ADP could result from their degradation into adenosine. α,β‐Methylene ADP appears to increase K⁺ permeability of the β‐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.