1996 Fiscal Year Final Research Report Summary
Introduction of glucose-responsive insulin secretion machinery to non-pancreatic beta cells
| Project/Area Number |
07557355
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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 | 試験 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Juntendo Univ., Dept.of Med. |
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Principal Investigator |
KAWAMORI Ryuzo Juntendo Univ., Dept of Med., Professor, 医学部, 教授 (00116021)
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| Co-Investigator(Kenkyū-buntansha) |
KAJIMOTO Yoshitaka Osaka Univ., 1st Dept of Med., Fellow, 医学部・附属病院, 医員
YAMASAKI Yoshimitsu Osaka Univ., 1st Dept of Med., Assistant Prof., 医学部, 助手 (40201834)
MOCHIZUKI Kentaro Juntendo Univ., Dept of Med., Assistant Prof., 医学部, 助手 (40266044)
ARISAKA Tomoyuki Juntendo Univ., Dept of Med., Assistant Prof., 医学部, 助手 (30266043)
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| Project Period (FY) |
1995 – 1996
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| Keywords | insulin gene / transcription factor / PDX-1 / gene therapy / molecular biology / pancreatic betacell |
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| Research Abstract |
Because the future gene therapy for diabetes would require the use of the non-pancreatic beta-cells (such as myocyte-derived cells) which express insulin in the glucose-dependent manner, we investigated whether the exogenous expression of a transcription factor PDX-1 in non-beta-cells could induce the beta-cell-specific gene expressions. As an initial step, we established alphaTC1 clone 6(alphaTC1.6)-derived stable transfectants expressing PDX-1 and examined the changes in the gene expression patterns in them. The exogenous expression of PDX-1 in alphaTC1.6 cells alone could induce islet amyloid polypeptide (IAPP) mRNA expression in the cells, but not the expression of insulin, glucokinase, or GLUT2 gene. However, when betacellulin was added to the medium, the PDX-1-expressing alphaTC1.6 cells but not the control alphaTC1.6 cells came to express insulin and glucokinase mRNAs. This did not occur with other growth factors such as epidermal growth factor (EGF), transforming growth factor alpha(TGFalpha) and IGF-l, GLUT2 mRNA remained undetectable in the PDX-1-expressing alphaTC1.6 cells. These observations demonstrate the potency of PDX-1 for the expression of the insulin, glucokinase, and IAPP genes and suggest that certain regulatory factors, which can partially be modified by betacellulin, also contribute to the beta-cell specificity of gene expression. Thus our present study provides support for the potential usefulness of both PDX-1 and betacellulin for the conversion of non-beta-cells to beta-cell-like cells.
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Research Products
(12 results)
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[Publications] Matsuoka T,Kajimoto Y,Watada H,Kaneto H,Kishimoto M,Umayahara Y,Fujitani Y,Kamada T,Kawamori R,and Yamasaki Y.: "Glycation-dependent, reactive oxygen species-mediated suppression of the insulin gene promoter activity in the HIT cells." J.Clin.Invest.99. 144-150 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kajimoto Y,Miyagawa J,Ishihara K,Okuyama Y,Fujitani Y,Itoh M,Yoshida H,Kashio T,Matsuoka T,Watada H,Hanafusa T,Yamasaki Y,Kamada T,Matsuzawa Y,and Hirano T.: "Pancreatic islet cells express BST-1, a CD38-like surface molecule having ADP-ribosyl cyclase activity." Biochem.Biophy.Res.Commun.219. 941-946 (1996)
Description
「研究成果報告書概要(欧文)」より
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