2026-10-14T17:53:02Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33538864 2026-10-01T17:35:22Z category_24454 portal_785 item_type_1 month_year_10_2026

Dynorphin A inhibits insulin secretion through opioid receptor–dependent modulation of β-cell Ca²⁺ dynamics Miranda Movahed (24762527) Mariam Gomareli (24762533) Ruy A. Louzada (16387834) Manuel Blandino-Rosano (6265892) Other biological sciences not elsewhere classified Beta Cell(s) Insulin Secretion Opioids Calcium Signaling G-Protein Coupled Receptor Opioids are classically associated with pain and reward, yet endogenous opioid peptides and their receptors are also expressed in pancreatic islets, where their physiological role remains unclear. Building on evidence that β-cells co-release 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 β-cell viability. Under dynamic perifusion, dynorphin A attenuates both first- and second-phase insulin release. Mechanistically, dynorphin A slows glucose-stimulated β-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: μ-opioid receptor blockade or β-cell–specific deletion abolishes inhibition in mouse islets, whereas δ-opioid receptor antagonism prevents dynorphin A–mediated inhibition in human islets. These findings define opioid receptor mechanisms underlying the inhibitory response to applied dynorphin A and reveal species-dependent receptor involvement in mouse and human islets. 2026-10-01T17:35:22Z Image Figure 10.2337/figshare.33538864.v1 https://figshare.com/articles/figure/_b_Dynorphin_A_inhibits_insulin_secretion_through_opioid_receptor_dependent_modulation_of_-cell_Ca_b_b_b_b_dynamics_b_/33538864 CC BY-NC-SA 4.0