δ-Cells Control a Subset of β-Cells in Mouse Pancreatic Islets

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 cytoplasmic free Ca2+ concentration ([Ca2+]i) imaging to interrogate the relative roles of paracrine and electrical control of β-cells by δ-cells. We confirm that optoactivation and optoinhibition of δ-cells stimulated and inhibited their electrical activity and somatostatin secretion, respectively. Unexpectedly, neither optoactivation nor optoinhibition of δ-cells had any effect on insulin secretion at 1 or 20 mmol/L glucose. Paradoxically, optoactivation of δ-cells at 6 mmol/L 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 mmol/L 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.

Optical activation or δ-cells stimulate somatostatin secretion. δ-Cell depolarization evokes β-cell action potential firing and insulin release. δ-Cell activation results in islet-wide synchronized β-cell cytoplasmic free Ca2+ concentration increases. δ-Cell inhibition aborts cytoplasmic free Ca2+ concentration oscillations in β-cell neighbors.