{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:06:33Z","timestamp":1790877993810,"version":"4.1.0"},"reference-count":0,"publisher":"American Diabetes Association","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases","award":["R01 DK132095"],"award-info":[{"award-number":["R01 DK132095"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Opioids are classically associated with pain and reward; however, endogenous opioid peptides and their receptors are also expressed in pancreatic islets, where their physiologic role remains unclear. Building on evidence indicating that \u03b2-cells corelease dynorphin A with insulin, we show that applied dynorphin A inhibits insulin secretion during glucose stimulation. Dynorphin A dose-dependently suppresses glucose-stimulated insulin secretion in mouse and human islets while preserving insulin content and \u03b2-cell viability. Under dynamic perifusion, dynorphin A attenuates both first- and second-phase insulin release. Mechanistically, dynorphin A slows glucose-stimulated \u03b2-cell Ca2+ oscillations in pancreatic slices, reducing oscillatory frequency while prolonging individual Ca2+ events. Notably, the receptor requirements for the inhibitory response to applied dynorphin A differ across species; \u03bc-opioid receptor blockade or \u03b2-cell\u2013specific deletion abolishes inhibition in mouse islets, whereas \u03b4-opioid receptor antagonism prevents dynorphin A\u2013mediated inhibition in human islets. These findings define the opioid receptor mechanisms underlying the inhibitory response to applied dynorphin A and reveal species-dependent receptor involvement in mouse and human islets.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>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 \u03b2-cell Ca2+ oscillations through an opioid receptor\u2013dependent, Na+\/K+-ATPase\u2013associated pathway. This response required \u03bc-opioid receptors in mouse \u03b2-cells and was pharmacologically consistent with \u03b4-opioid receptor involvement in human islets, defining species-dependent receptor mechanisms for the acute response to dynorphin A.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db26-0224","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:38:12Z","timestamp":1790876292000},"update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Dynorphin A Inhibits Insulin Secretion Through Opioid Receptor\u2013Dependent Modulation of \u03b2-Cell Ca2+ Dynamics"],"prefix":"10.2337","author":[{"given":"Miranda","family":"Movahed","sequence":"first","affiliation":[{"name":"1Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Miller School of Medicine, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Gomareli","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Miller School of Medicine, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruy A.","family":"Louzada","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Miller School of Medicine, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1712-8233","authenticated-orcid":false,"given":"Manuel","family":"Blandino-Rosano","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Miller School of Medicine, University of Miami, Miami, FL"},{"name":"2Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2026,10,1]]},"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/doi\/10.2337\/db26-0224\/897731\/db260224.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/doi\/10.2337\/db26-0224\/897731\/db260224.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:38:12Z","timestamp":1790876292000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/doi\/10.2337\/db26-0224\/172712\/Dynorphin-A-Inhibits-Insulin-Secretion-Through"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":0,"URL":"https:\/\/doi.org\/10.2337\/db26-0224","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]},"article-number":"db260224"}}