Dopamine D2 Receptor-Mediated Regulation of Pancreatic ? Cell Mass.

ABSTRACT: Understanding the molecular mechanisms that regulate ? cell mass and proliferation is important for the treatment of diabetes. Here, we identified domperidone (DPD), a dopamine D2 receptor (DRD2) antagonist that enhances ? cell mass. Over time, islet ? cell loss occurs in dissociation cultures, and this was inhibited by DPD. DPD increased proliferation and decreased apoptosis of ? cells through increasing intracellular cAMP. DPD prevented ? cell dedifferentiation, which together highly contributed to the increased ? cell mass. DRD2 knockdown phenocopied the effects of domperidone and increased the number of ? cells. Drd2 overexpression sensitized the dopamine responsiveness of ? cells and increased apoptosis. Further analysis revealed that the adenosine agonist 5'-N-ethylcarboxamidoadenosine, a previously identified promoter of ? cell proliferation, acted with DPD to increase the number of ? cells. In humans, dopamine also modulates ? cell mass through DRD2 and exerts an inhibitory effect on adenosine signaling.

SUBMITTER: Sakano D 

PROVIDER: S-EPMC4944721 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature