2002 Fiscal Year Final Research Report Summary
Analysis of Pancreatic B-Cell Development and an Animal Model of Regeneration Therapy for Diabetes Mellitus Using Transgenic Mice
| Project/Area Number |
13671194
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | The University of Tokushima |
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Principal Investigator |
YAMAOKA Takashi The University of Tokushima, Institute for Genome Research, Associate Professor, ゲノム機能研究センター, 助教授 (40263826)
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| Co-Investigator(Kenkyū-buntansha) |
SUGINO Hiromu The University of Tokushima, Instiute for Enzyme Research, Professor, 分子酵素学研究センター, 教授 (50211305)
NOJI Sumihare The University of Tokushima, Department of Biological Science and Technology, Professor, 工学部, 教授 (40156211)
ITAKURA Mitsuo The University of Tokushima, Instiute for Genome Research, Professor, ゲノム機能研究センター, 教授 (60134227)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Pancreatic islets / Pancreatic B cells / Transgenic mouse / Cdk4 / Activin / HB-EGF / Regenerative medicine / Diabetes mellitus |
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| Research Abstract |
In transnic mice expressing active Cdk4 mutant driven by the insulin promoter, B-cell area was remarkably increased by B-cell proliferation up to half of the whole pancreas area. Proliferated B cells were highly differentiated: they contained a great amount of insulin seretory granules and GLUT2 were expressed on their cell membrane. Cdk4-transgenic mice showed better glucose tolerance than normal control mice did, but neither insulinoma nor hypoglycemic symptoms occurred. Because activation of Cdk4 induced the proliferation of highly differentiated B cells. It is suggested that Cdk4 is a target molecule of regeneration therapy for diabetes mellitus.
Both transgenic mice expressing dominant negative activin receptor and transgenic mice expressing activin B by the Pdx1 promoter showed islet hypoplasia and developed diabetes, suggestng that appropriate activin signaling is necessary for normal development of B cells. Therefore, apropriate concentration and timing of activin admistration should be considered for the differentiation of ES cells into pancreatic B cells.
Both transgenic mice expressing dominant negative activin receptor and transgenic mice expressing HB-EGF by the Pdx1 promoter showed the dilation of pancreatic duct and bile duct. These results indicate that the proliferaion of these ductal epothelia is regulated by activin and HB-EGF. HB-EGF is probably useful for effective expansion of cultured pancreatic ductal cells as the source of B-cell precursor.
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