| Project/Area Number |
12557089
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Endocrinology
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| Research Institution | Osaka University |
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Principal Investigator |
MIYAGAWA Jun-ichiro Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (00127721)
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| Co-Investigator(Kenkyū-buntansha) |
IMAGAWA Akihisa Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
YAMAGATA Kazuya Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70324770)
YAMAMOTO Koji Osaka University Hospital, Assistant Professor, 医学部・附属病院, 助手 (60304060)
東山 繁樹 大阪大学, 医学部, 助教授 (60202272)
MORIWAKI Makoto Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 2001: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥6,400,000 (Direct Cost: ¥6,400,000)
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| Keywords | β cell / Diabetes mellitus / Regeneration / Differentioation / Betacellulin / Gene therapy / Growth factor / Heparin-binding EGF-like growth factor (HB-EGF) / ベータセルリン |
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| Research Abstract |
This research was undertaken to establish the new therapy for diabetes mellitus especially for βcell-depleted type of diabetes. We reported that Betacellulin and Heparin-binding EGF-like growth factor (HB-EGF), both of which belong to EGF family, are expressed abundantly in human pancreas, especially developing fetal pancreas, and that recombinant human betacellulin, has a potency to induce differentiation of βcell from non-β pancreatic exocrine cell line. To confirm this effect of betacellulin in vivo, we next demonstrated that recombinant human betacellulin ameliorated glucose intolerance in diabetic mice model induced by selective perfusion of alloxan. These results indicate that betacellulin and HB-EGF may act as a growth and/or differentiation factor in the pancreas.
Based on these evidence, we intend to develop the new gene therapy for βcell regeneration by non-invasive method of endoscopic retrograde injection into pancreatic duct. We tried to induce βcell neogenesis from duct ce
… More
lls by injecting adenovirus vector containing LacZ or genes of putative β cell differentiation factors such as Betacellulin and Heparin-binding EGF-like growth factor in mice. We succeeded in inducing the expression of LacZ mainly in duct cells by injecting LacZ-containing adenovirus into duct from the orifice of pancreatic duct in the duodenum without any serious side effect, suggesting that this method of regeneration therapy for diabetes is applicable to larger animals including human. As a next step, we tried to induce Betacellulin and HB-EGF genes in pancreatic duct cells using adenovirus vector. Both genes could be expressed in duct cells, and neogenesis of endocrine cells including β cells from ducts was observed, but expression levels of these gene products appeared to be not enough to elevate the insulin content significantly. It is necessary to improve the expression level of such genes to develop the new gene therapy for diabetes by the method of endoscopic retrograde injection of adenovirus vectors containing such genes of β cell differentiation factors into pancreatic duct. Less
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