We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Functional genetics reveals the contribution of delta opioid receptor to type 2 diabetes and beta-cell function.
- Authors
Meulebrouck, Sarah; Merrheim, Judith; Queniat, Gurvan; Bourouh, Cyril; Derhourhi, Mehdi; Boissel, Mathilde; Yi, Xiaoyan; Badreddine, Alaa; Boutry, Raphaël; Leloire, Audrey; Toussaint, Bénédicte; Amanzougarene, Souhila; Vaillant, Emmanuel; Durand, Emmanuelle; Loiselle, Hélène; Huyvaert, Marlène; Dechaume, Aurélie; Scherrer, Victoria; Marchetti, Piero; Balkau, Beverley
- Abstract
Functional genetics has identified drug targets for metabolic disorders. Opioid use impacts metabolic homeostasis, although mechanisms remain elusive. Here, we explore the OPRD1 gene (encoding delta opioid receptor, DOP) to understand its impact on type 2 diabetes. Large-scale sequencing of OPRD1 and in vitro analysis reveal that loss-of-function variants are associated with higher adiposity and lower hyperglycemia risk, whereas gain-of-function variants are associated with lower adiposity and higher type 2 diabetes risk. These findings align with studies of opium addicts. OPRD1 is expressed in human islets and beta cells, with decreased expression under type 2 diabetes conditions. DOP inhibition by an antagonist enhances insulin secretion from human beta cells and islets. RNA-sequencing identifies pathways regulated by DOP antagonism, including nerve growth factor, circadian clock, and nuclear receptor pathways. Our study highlights DOP as a key player between opioids and metabolic homeostasis, suggesting its potential as a therapeutic target for type 2 diabetes. Opioid use impacts metabolic homeostasis, although the mechanisms remain elusive. Here, the authors explore the OPRD1 gene (encoding the delta opioid receptor, DOP) to understand its impact on type 2 diabetes and highlight DOP as a key player between opioids and metabolic homeostasis.
- Subjects
TYPE 2 diabetes; NERVE growth factor; PANCREATIC beta cells; ISLANDS of Langerhans; METABOLIC disorders
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-51004-6