Dopamine D2 Receptor-Mediated Regulation of Pancreatic β Cell Mass

被引：29
作者：
Sakano, Daisuke [1 ]
Choi, Sungik [2 ]
Kataoka, Masateru [2 ]
Shiraki, Nobuaki [1 ]
Uesugi, Motonari [3 ]
Kume, Kazuhiko [4 ]
Kume, Shoen [1 ]
机构：
[1] Tokyo Inst Technol, Sch Life Sci & Technol, Dept Life Sci & Technol, Midori Ku, 4259-B-25 Nagatsuta, Yokohama, Kanagawa 2268501, Japan
[2] Kumamoto Univ, Inst Mol Embryol & Genet, Div Stem Cell Biol, Honjo 2-2-1, Kumamoto 8600811, Japan
[3] Kyoto Univ, Inst Integrated Cell Mat Sci, Inst Chem Res, Dept Biol Chem, Uji, Kyoto 6110011, Japan
[4] Nagoya City Univ, Grad Sch Pharmaceut Sci, Dept Neuropharmacol, 3-1 Tanabe St, Nagoya, Aichi 4678603, Japan
来源：
STEM CELL REPORTS | 2016年 / 7卷 / 01期
关键词：
REGENERATING RAT PANCREAS; ADULT-MOUSE PANCREAS; INSULIN-SECRETION; STREPTOZOTOCIN TREATMENT; ADENOSINE A(2A); IN-SITU; EXPRESSION; ISLET; DIFFERENTIATION; PROLIFERATION;
D O I：
10.1016/j.stemcr.2016.05.015
中图分类号：
Q813 [细胞工程];
学科分类号：
摘要：
Understanding the molecular mechanisms that regulate beta cell mass and proliferation is important for the treatment of diabetes. Here, we identified domperidone (DPD), a dopamine D2 receptor (DRD2) antagonist that enhances beta cell mass. Over time, islet beta cell loss occurs in dissociation cultures, and this was inhibited by DPD. DPD increased proliferation and decreased apoptosis of beta cells through increasing intracellular cAMP. DPD prevented beta cell dedifferentiation, which together highly contributed to the increased beta cell mass. DRD2 knockdown phenocopied the effects of domperidone and increased the number of b cells. Drd2 over-expression sensitized the dopamine responsiveness of beta cells and increased apoptosis. Further analysis revealed that the adenosine agonist 50-N-ethylcarboxamidoadenosine, a previously identified promoter of beta cell proliferation, acted with DPD to increase the number of beta cells. In humans, dopamine also modulates beta cell mass through DRD2 and exerts an inhibitory effect on adenosine signaling.
引用
收藏
页码：95 / 109
页数：15
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