| Project/Area Number |
21790285
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Kyushu University |
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Principal Investigator |
INADA Akari Kyushu University, 大学院・医学研究院, 准教授 (50448429)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 糖尿病 / β細胞 / 前駆細胞 / 膵管 / 分化 |
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| Research Abstract |
We further studied the mechanism of differentiation of ductal cells to β cells. Although Pdx-1 is mainly restricted to β cells in the adult pancreas to regulate several β-cell specific genes, the increased Pdx-1 protein level in the duct has been reported in human obesity and the rodent regeneration mode. This coincident of increased Pdx-1 protein level imply that the regeneration mode the pancreas recapitulates embryonic development and that neogenesis contributes to the increased islet mass. To test our hypothesis that Pdx-1 expression in the duct could be critical factor for the differentiation of ductal cells to β cells, we generated duct-specific Pdx-1 knockout mice by crossing the CAII-Cre mice to Pdx-1flE2/flE2 mice, in which Pdx-1 expression in the duct was knocked out around the birth. Inactivation of Pdx-1 in the duct resulted in reduced β cells in normal growth which caused hyperglycemia and glucose tolerance. Moreover, in the regeneration study new β-cell formation was rarely seen in the adult. Thus, the activation of Pdx-1 in the duct is required for differentiation, and these differentiated β cells contribute to intensive β-cell growth in neonatal period and injury in the adult. Our study provides clear evidence of a compensatory function of a ductal-origin β cell.
These findings should encourage further exploration of pancreatic duct cells as a source for islet regeneration. Further attention on expansion and differentiation of these cells may facilitate β-cell replacement therapy for diabetes.
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