Dynorphin A Inhibits Insulin Secretion Through Opioid Receptor-Dependent Modulation of β-Cell Ca2+ Dynamics.

The role of endogenous opioid signaling within pancreatic islets remains poorly defined. We investigated whether dynorphin A regulates insulin secretion and characterized the receptor requirements for the acute response to applied dynorphin A in mouse and human islets. Applied dynorphin A suppressed glucose-stimulated insulin secretion by remodeling β-cell Ca2+ oscillations through an opioid receptor-dependent, Na+/K+-ATPase-associated pathway. This response required μ-opioid receptors in mouse β-cells and was pharmacologically consistent with δ-opioid receptor involvement in human islets, defining species-dependent receptor mechanisms for the acute response to dynorphin A.