2013 Fiscal Year Final Research Report
Small compounds promote differentiation of functional insulin producing cells
| Project/Area Number |
24790949
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Endocrinology
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| Research Institution | Kumamoto University |
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Principal Investigator |
SAKANO Daisuke 熊本大学, 発生医学研究所, 助教 (40571039)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | ES・iPS細胞 / 膵β細胞 / インスリン / 糖尿病 / 低分子化合物 / モノアミン |
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| Research Abstract |
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 compound
library. 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.
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[Journal Article] VMAT2 identified as a regulator of late-stage beta cell differentiation2014
Author(s)
Sakano D , Shiraki N , Kikawa K , Yamazoe T, Kataoka M, Umeda K, Araki K, Mao D, Matsumoto S, Nakagata N, Andersson O, Stainier D, Endo F, Kume K, Uesugi M and Kume S
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Journal Title
Nature Chem. Biol
Volume: 10(2)
Pages: 141-8
Peer Reviewed
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[Presentation] VMAT2 identified as a regulator of late-stage β-cell differentiation2013
Author(s)
Sakano D, Shiraki N, Kikawa K, Yamazoe T, Kataoka M, Umeda K, Araki K, Mao D, Matsumoto S, Nakagata N, Andersson O, Stainier D, Endo F, Kume K, Uesugi M and Kume S
Organizer
ISSCR 11th annual meeting
Place of Presentation
Boston, USA
Year and Date
20130612-15
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