Dopamine D2 Receptor-Mediated Regulation of Pancreatic β Cell Mass

• 上杉, 志成

• Choi, Sungik

• Kataoka, Masateru

• Shiraki, Nobuaki

• Uesugi, Motonari

• Kume, Kazuhiko

• Kume, Shoen

抄録

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

収録刊行物

• Stem cell reports

  Stem cell reports 7 (1), 95-109, 2016-07-12

  Elsevier BV

詳細情報

• CRID: 1050282810812467584
• NII論文ID: 120005829378
• ISSN: 22136711
• HANDLE: 2433/216336
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles