Pulsatile insulin release into the portal vein is critically dependent on entrainment of the islets in the pancreas into a common oscillatory phase. Because the pulses reflect periodic variations of the cytoplasmic Ca2+ concentration ([Ca2+]i), we studied whether the neurotransmitters adenosine triphosphate (ATP) and acetylcholine promote synchronization of [Ca2+]i oscillations between islets lacking contact.Methods
Medium-sized and small mouse islets and cell aggregates were used for measuring [Ca2+]i with the indicator fura-2.Results
Exposure to acetylcholine resulted in an initial [Ca2+]i peak followed by disappearance of the [Ca2+]i oscillations induced by 11-mmol/L glucose. The effect of ATP was often restricted to an elusive [Ca2+]i peak. The incidence of distinct [Ca2+]i responses to ATP increased under conditions (accelerated superfusion, small islets, or cell aggregates) intended to counteract purinoceptor desensitization owing to intercellular accumulation of ATP. Attempts to imitate neural activity by brief (15 seconds) exposure to ATP or acetylcholine resulted in temporary synchronization of the glucose-induced [Ca2+]i oscillations between islets lacking contact.Conclusions
The data support the idea that purinergic signaling has a key role for coordinating the oscillatory activity of the islets in the pancreas, reinforcing previous arguments for the involvement of nonadrenergic, noncholinergic neurons.