Research Project
Grant-in-Aid for Young Scientists (B)
Despite numerous efforts, it is still difficult to efficiently produce mature insulin-secreting beta cell from ES cells. Here, we focused on the late stages of the differentiation and performed a cell-based screening of chemical compoundlibrary. We identified reserpine as a small molecule that inhibits vesicular monoamine transporter 2 (VMAT2)-mediated secretion of monoamine that promoted differentiation of Pdx1-positive progenitors into insulin-expressing cells. Our analyses suggest that one of the VMAT2-controlled monoamines, dopamine, serotonin and histamine negatively regulates beta cell differentiation. Exogenous addition of a cell-permeable cAMP analogue dBu-cAMP canceled these inhibitory effects on beta cell differentiation and synergized with VMAT2 inhibition. The ES cell derived beta cells showed glucose-sensitive insulin secretion ability, and reversed hyperglycemia upon engraftment into AKITA diabetic mice.
All 2014 2013 2012 Other
All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (11 results) (of which Invited: 1 results) Book (3 results) Remarks (5 results)
Nature Chem. Biol
Volume: 10(2) Pages: 141-8
40020189460
Nat. Chem. Biol.
Volume: 10 Issue: 2 Pages: 141-148
10.1038/nchembio.1410
http://www.kumamoto-u.ac.jp/daigakujouhou/kouhou/pressrelease/2013_file/release131216.pdf#search='%E8%86%B5%CE%B2%E7%B4%B0%E8%83%9E%E3%81%AE%E5%88%86%E5%8C%96%E3%82%92+%E5%B0%8F%E8%83%9E%E4%BD%93'
http://www.imeg.kumamoto-u.ac.jp/newpress/np67.html
http://www.kumamoto-u.ac.jp/whatsnew/seimei/20131216