| 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 |
| Source: |
Nature Communications; 8/5/2024, Vol. 15 Issue 1, p1-12, 12p |
| Subject Terms: |
TYPE 2 diabetes, NERVE growth factor, PANCREATIC beta cells, ISLANDS of Langerhans, METABOLIC disorders |
| 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. [ABSTRACT FROM AUTHOR] |
|
Copyright of Nature Communications is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |
