δ-cells control a subset of β-cells in mouse pancreatic islets

<p dir="ltr">Somatostatin is a powerful inhibitor of insulin secretion and β-cell electrical activity but the effects are weak in intact islets, possibly because of high intraislet somatostatin levels. We used optogenetics in conjunction with hormone secretion measurements, electrophysiology and [Ca2+]i imaging to interrogate the relative roles of paracrine and electrical control of β-cells by δ-cells. We confirm that optoactivation and -inhibition of δ-cells stimulated and inhibited their electrical activity and somatostatin secretion, respectively. Unexpectedly, neither optoactivation nor -inhibition of δ-cells had any effect on insulin secretion at 1 or 20 mM glucose. Paradoxically, optoactivation of δ-cells at 6 mM glucose increased insulin secretion by 113%, an effect that correlated with β-cell action potential firing. In [Ca2+]i imaging experiments, optoactivation of δ-cells induced islet-wide β-cell [Ca2+]i transients and synchronized the oscillatory pattern induced by 7 mM glucose. Conversely, optoinhibition of δ-cells and somatostatin secretion reduced rather than increased β-cell electrical activity and [Ca2+]i in the <10% of β-cells situated <20 µm from δ-cells. We propose that δ-cells, in addition to subserving an inhibitory paracrine effect, play a role in the rapid propagation of electrical signals across the islet, possibly contributing to the coordination of β-cell activity.</p>