Mechanism of differentiation and growth of pancreatic βcells by newly identified growth factor, NTAK, and its application for regenerative medicine in diabetes mellitus
| Project/Area Number |
18591006
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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 | Hyogo College of Medicine |
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Principal Investigator |
MIYAGAWA Jun-ichiro Hyogo College of Medicine, Faculty of Medicine, Associate Professor (00127721)
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| Co-Investigator(Kenkyū-buntansha) |
NAMBA Mitsuyoshi Hyogo College of Medicine, Faculty of Medicine, Professor (00183533)
HAMAGUCHI Tomoya Hyogo College of Medicine, Faculty of Medicine, Assistant Professor (60330461)
KONYA Hiroyuki Hyogo College of Medicine, Faculty of Medicine, Assistant Professor (50340956)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,410,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | NTAK / Pancreatic β cell / growth factor / proliferation / differentiation / development / regeneration / diabetes mellitus |
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| Research Abstract |
We have been studied on the mechanism of regeneration and differentiation, and apoptosis of pancreatic β cells to develop the new therapeutic approach to diabetes mellitus. In this research, we investigated the possible involvement of neural-and thymus-derived activator for ErbB kinases (NTAK), newly identified growth factor which belongs to the EGF family, and CD 9, one of the modulators of EGF family signal transduction. We demonstrated the adult and fetal pancreas produced NTAK which is localized in β cells and fetal pancreatic epithelial cells including endocrine precursor cells, respectively. CD-9 also expressed on islet cells. These results suggested that NTAK and CD-9 may be involved in the mechanism of differentiation and/or proliferation of pancreatic β cells in addition to the development of pancreas.
In vitro peptide study of NTAK revealed that partial sequence of peptides of NTAK showed the activity of proliferation, while some other part of peptide sequence inhibited the proliferation of β cell line, MIN6 cells, suggesting that NTAK signal transduction may be involved in both positive and negative (apoptotic?) regulatory pathways for β cell proliferation and/or differentiation. Further study is necessary to elucidate the detailed signal transduction pathway(s) of NTAK in pancreatic β cells.
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Report
(3 results)
Research Products
(40 results)
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[Journal Article] Expression of HNF2008
Author(s)
Nammo T., Yamagata K., Tanaka T., Kodama T., Sladek F. M., Fukui K., Katsube F., Sato Y., Miyagawa J., Shimomura I.
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Journal Title
Gene Expr Patterns 8(2)
Pages: 96-106
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Clinical significance of circulating hepatocyte growth factor, a new risk marker of carotid atherosclerosis in patients with Type 2 diabetes.2007
Author(s)
Satani K., Konya H., Hamaguchi T., Umehara A., Katsuno T., Ishikawa T., Kohri K., Hasegawa Y., Suehir, A., Kakishita K., Namba M.
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Journal Title
Diabet Med 23
Pages: 617-622
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Macrophages and dendritic cells infiltrating islets with or without beta cells produce tumor necrosis factor-α in patients with recent-onset type 1 diabetes.2007
Author(s)
Uno S., Imagawa A., Okita K., Sayama K., Moriwaki M., Iwahashi H., Yamagata K., Tamura S., Matsuzawa Y., Hanahusa T., Miyagawa J., Shimomura I.
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Journal Title
Diabetologia 50
Pages: 596-601
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Continuous stimulation of human glucagon-like peptide-1(7-36) amide in a mouse model(NOD) delays onset of autoimmune typel diabetes.2007
Author(s)
Zhang J., Tokui Y., Yamagata K., Kozawa J., Sayama K., Iwahashi H., Okita K., Miuchi M., Konya H., Hamaguchi T., Namba M., Shimomura I., Miyagawa J.
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Journal Title
Diabetologia 50
Pages: 1900-1909
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The tetraspanin CD9 modulates epidermal growth factor receptor2007
Author(s)
Murayama Y., Shinomura Y., Oritani K., Miyagawa J., Yoshida H., Nishida M., Katsube F., Shiraga M., Miyazaki T., Nakamoto T., Tsutsui S., Tamura S., Higashiyama S., Shimomura I., Hayashi N.
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Journal Title
J Cell Physiol 216(1)
Pages: 135-143
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Macrophages and dendritic cells infiltrating islets with or without beta cells produce tumor necrosis factor-α in patients with recent-onset type 1 diabetes.2007
Author(s)
Uno S., Imagawa A., Okita K., Sayama K., Moriwaki M., Iwahashi H., Yamagata K., Tamura S., Matsuzawa Y., Hanahusa T., Miyagawa J., Shimomura I.
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Journal Title
Diabetologia 50・3
Pages: 596-601
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[Journal Article] Hepatocyte nuclear 4-α is essential for glucose-stimulated insulin secretion by pancreatic β-cells.2006
Author(s)
Miura A., Yamagata K., Kakei M., Hatakeyama H., Takahashi N., Fukui K., Nammo T., Yoneda K., Inoue Y., Sladek F. M., Magnuson M. A., Kasai H., Miyagawa J., Gonzalez F. J., Shimomura I.
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Journal Title
J Biol Chem 281(8)
Pages: 5246-5257
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Neogenesis and proliferation of β-cells induced by human betacellulin gene transduction via retrograde pancreatic duct injection of an adenovorus vector.2006
Author(s)
Tokui Y., Kozawa J., Yamagata K., Zhang J., Ohmoto H., Tochino Y., Okita K., Iwahashi H., Namba M., Shimomura I., Miyagawa J.
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Journal Title
Biochem Biophys Res Commun 350
Pages: 987-993
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Hepatocyte nuclear 4-α is essential for glucose-stimulated insulin secretion by pancreatic β-cells.2006
Author(s)
Miura A., Yamagata K., Kakei M., Hatakeyama H., Takahashi N., Fukui K., Nammo T., Yoneda K., Inoue Y., Sladek F.M., Magnuson M.A., Kasai H., Miyagawa J., Gonzalez F.J.
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Journal Title
J Biol Chem 281・8
Pages: 5246-5257
Related Report
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[Journal Article] Clinical significance of circulating hepatocyte growth factor, a new risk marker of carotid atherosclerosis in patients with Type 2 diabetes.2006
Author(s)
Satani, K., Konya, H., Hamaguchi, T., Umehara, A., Katsuno, T., Ishikawa, T., Kohri, K., Hasegawa, Y., Suehiro, A., Kakishita, K., Namba, M.
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Journal Title
Diabet Med 23
Pages: 617-622
Related Report
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