Research of prevention of type 1 diabetes by thiazolidine derivative.
| Project/Area Number |
17590931
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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 | Kobe University |
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Principal Investigator |
NAGATA Masao Kobe University, Graduate School of Medicine, Associate Professor (70294220)
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| Co-Investigator(Kenkyū-buntansha) |
YOKONO Koichi Kobe University, Graduate School of Medicine, Professor (50144580)
MORIYAMA Hiroaki Kobe University, Graduate School of Medicine, COE Research Fellow (70372646)
NAKAMURA Masato Kyoto Prefectual University of Medicine, 大学院・医学系研究科, Associate Professor (40227921)
TAKAHASHI Kazuma Iwate Medical University, 医学部, Lecturer (60292215)
KAWAMURA Tomoyuki Osaka City University, Graduate School of Medicine, Assistant Professor (60271186)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,680,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Type 1 diabetes / Thiazolidine derivative / Pioglitazone / Dendritic cells / NOD mouse / ピオグリタゾン / 緩徐進行型1型糖尿病 / NKT細胞 / チアゾリン誘導体 / 液体食事負荷試験 |
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| Research Abstract |
1. Prevention of type 1 diabetes by pioglitazone in NOD mice
Oral administration of pioglitazone prevented overt diabetes in female NOD mice not only from 4 weeks of age but also from 10 weeks of age when most of pancreas already showed intra-islet cellar infiltration. Transfer experiments using spleen cells to NOD-scid mice revealed that effector activity was decreased, whereas immuno-regulatory activity was not enhanced by pioglitazone administration_ Flow cytometric analysis showed that CD25^+ CD4^+ T cells were not increased but NKT cells were increased by pioglitazone. Cell surface of dendritic cells showed the increased expression of CD80, co-stimulatory molecule B7-1, and CD1d. These results suggested that the characteristics of dendritic cells were changed by pioglitazone and enhanced NKT cells, leading the autoimmune response to pancreatic β cells. Our study revealed that modification of dendritic cells is one of powerful strategy to prevent type 1 diabetes.
2. Prevention of the progression of pancreatic β cell destruction in human type 1 diabetes
To evaluate the effect of pioglitazone on human type 1 diabetes, we administered pioglitazone with intensive insulin therapy to acute type 1 diabetes. During 2 years follow up, three patients with pioglitazone 30mg/day showed progressive decrease of serum C-peptide level and required much more dose of insulin to control blood sugar. Furthermore, one slowly progressive patient became keto-acidosis after 23 months administration of pioglitazone. These results suggests that at least ordinal dose of pioglitazone cannot inhibit progression of β cell destruction in human type 1 diabetes.
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] Prevention of recurrent but not spontaneous autoimmune diabetes by transplanted NOD islets adenovirally transduced with immunomodulating molecules2008
Author(s)
Sakata, M, Yasuda, H, Moriyama, H, Yamada, K, Kotani, R, Kurohara, M, Okumachi, Y, Kishi, M, Arai, T, Hara, K, Hamada, H, Yokono, K, Nagata, M
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Journal Title
Diabetes Res Clin Pract 80(3)
Pages: 352-9
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Modification of the Rb-binding Domain of Replication-Competent Adenovirus Vector Enhances Cytotoxicity Against Human Esophageal Cancers via NF-kB Activity2007
Author(s)
Yamada, K, Moriyama, H, Yasuda, H, Hara, K, Maniwa, Y, Hamada, H, Koichi, Yokono, Nagata, M
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Journal Title
Hum Gene Ther 18(5)
Pages: 389-400
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Insulin as a T cell antigen in type 1 diabetes supported by the evidence from the insulin knockout NOD mice2007
Author(s)
Moriyama, H., Nagata, M., T., Arai, Y., Okumachi, K., Yamada, R., Kotani, H., Yasuda, K., Hata, K, Yokono
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Journal Title
Diabetes Res Clin Pract S155-160
Description
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[Journal Article] Low-dose warfarin functions as an immunomodulator to prevent cyclophosphamide-induced NOD diabetes
Author(s)
Kurohara, M, Yasuda, H, Moriyama, H, Sakata, M, Yamada, K, Kotani, R, Nakayama, M, Hara, K, Yokono, K, Nagata, M
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Journal Title
Kobe J. Med. Sci (in press)
NAID
Description
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