Regeneration of pancreatic beta-cells that secret insulin in response to glucose stimulation
| Project/Area Number |
17590937
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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 | Kagawa University |
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Principal Investigator |
ISHIDA Toshihiko Kagawa University, Faculty of Medicine, Professor, 医学部, 教授 (50159737)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUMITSU Hiroshi Kagawa University, Faculty of Medicine, Assistant Professor, 医学部, 助教授 (20237077)
MURAO Koji Kagawa University, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (20291982)
OHNISHI Hiroaki Kagawa University, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (90223891)
IMACHI Hitomi Kagawa University, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (80380187)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | insulin / PREB / stem cell / pancreatic beta-cell / glucose / regeneration / gene transcription / Diabetes mellitus / インスリン / グルコース / 転写調節 |
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| Research Abstract |
PREB (prolactin regulatory element binding) protein has been identified as a factor that regulates prolactin promoter activity in rat anterior pituitary. PREB is located not only in the anterior pituitary but also in pancreas, however its role in pancreas is not known. Therefore, we examined the role of PREB in insulin gene expression. To analyze the effects of PREB on insulin gene transcription, we employed the reporter gene assay and EMSA. In the cells expressing or knocked down the PREB, insulin expression and secretion were determined. PREB was located mainly in nuclei of rat pancreatic β-cells and its cell line, INS-1. A nuclear extract of INS-1 cells contained material that was recognized by PREB antiserum. Furthermore, this nuclear extract contained insulin promoter binding activity that was super-shifted by PREB antiserum in EMSA studies. In the INS-1 cells, the co-expression of PREB and the insulin promoter induced activity of the latter. The addition of glucose to the cells increased PREB expression. Deletional analysis of the insulin promoter showed that A3, a glucose-responsive cis-element in the insulin promoter mediated the transcriptional effect of PREB. Additionally, synthesized PREB bound the A3 element by EMSA, while a mutant of this motif in the insulin promoter abrogated the effect of PREB. Furthermore, cells expressing or knock-down PREB exhibited increased or decreased insulin expression, respectively. These results demonstrate that PREB may contribute to the regulation of insulin gene transcription and insulin secretion in response to glucose stimulation.
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Report
(3 results)
Research Products
(14 results)
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[Journal Article] Pancreatic Glucokinase is Activated by Insulin-like Growth Factor-I2007
Author(s)
Yoshida K, Murao K, Imachi H, Cao WM, Yu X, Li J, Ahmed RA, Kitanaka N, Wong NCW, Unterman TG, Magnuson MA, Ishida T.
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Journal Title
Endocrinology 148
Pages: 2904-2913
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] High-density lipoprotein is a potential growth factor for adrenocortical cells2006
Author(s)
Murao K, Imachi H, Cao WM, Yu X, Li L, Yoshida K, Ahmed RAM, Matsumoto K, Nishiuchi T, Wong NCW, Ishida T.
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Journal Title
Biochem Biophys Res Commun. 344
Pages: 226-232
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Platelet derived growth factor regulates ABCA1 expression in vascular smooth muscle cells.2006
Author(s)
Nagao S, Murao K, Imachi H, Cao WM, Yu X, Li J, Matsumoto K, Nishiuchi T, Ahmed RA, Wong NC, Ueda K, Ishida T.
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Journal Title
FEBS Lett. 580
Pages: 4371-4376
Description
「研究成果報告書概要(欧文)」より
Related Report
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