Molecular mechanism for pancreatic beta-cell glucose toxicity
Project/Area Number |
21591135
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Metabolomics
|
Research Institution | Osaka University |
Principal Investigator |
KANETO Hideaki 大阪大学, 医学系・研究科, 准教授 (80448034)
|
Co-Investigator(Kenkyū-buntansha) |
TAKA-AKI Matsuoka 大阪大学, 医学系・研究科, 助教 (10379258)
松久 宗英 徳島大学, 糖尿病臨床研究開発センター, 教授 (60362737)
|
Project Period (FY) |
2009 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 糖尿病 / 膵β細胞 / ブドウ糖毒性 / 酸化ストレス / 転写因子 / インスリン合成 / インスリン分泌 / インスリン / インクレチン / インスリン抵抗性 / フェントン反応 / 銅イオン / 銅キレート剤 |
Research Abstract |
Progressive beta-cell dysfunction and loss of beta-cell mass are fundamental pathogenic features of type 2 diabetes. To examine if anti-diabetic reagents, such as insulin, pioglitazone(pio), and alogliptin(alo), have protective effects on beta-cell mass and function in vivo, we treated obese diabetic db/ db mice with these reagents. As the results, combination therapy with pio and alo almost completely normalized beta-cell function in vivo, which was comparable with insulin treatment. Reactive oxygen species(ROS) are induced under diabetic conditions and are likely associated with the development of type 2 diabetes. It is also known that ROS production is facilitated in the presence of copper ion through the Fenton reaction. To examine the involvement of copper ion in the pathogenesis of type 2 diabetes, treatedobese diabetic db/ db mice with a copper chelating agent. As the results, copper chelating agent reduced ROS levels and decreased blood glucose level.
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Report
(4 results)
Research Products
(66 results)
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[Journal Article] Effect of alogliptin, pioglitazone and glargine on pancreaticβ-cells in diabetic db/ db mice2011
Author(s)
Kawashima, S., Matsuoka, T., Kaneto, H., Tochino, Y., Kato, K., Yamamoto, K., Yamamoto, T., Matsuhisa, M., and Shimomura, I.
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Journal Title
Biochem. Biophys. Res. Commun
Volume: 404
Pages: 534-540
Related Report
Peer Reviewed
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[Journal Article] Regulation of MafA expression in pancreaticβ-cells in db/ db mice with diabetes2010
Author(s)
Matsuoka, T., Kaneto, H., Miyatsuka, T., Yamamoto, T., Yamamoto, K., Kato, K., Shimomura, I., Stein, R., and Matsuhisa, M.
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Journal Title
Diabetes
Volume: 59
Pages: 1709-1720
Related Report
Peer Reviewed
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[Journal Article] Role of copper ion in the pathogenesis of type 2 diabetes2009
Author(s)
Tanaka, A., Kaneto, H., Miyatsuka, T., Yamamoto, K, Yoshiuchi, K., Yamasaki, Y., Shimomura, I., Matsuoka, T., and Matsuhisa, M.
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Journal Title
Endocr. J
Volume: 56
Pages: 699-706
NAID
Related Report
Peer Reviewed
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[Journal Article] Role of MafA in pancreaticβ-cells2009
Author(s)
Kaneto, H., Matsuoka, T., Kawashima, S., Yamamoto, K., Kato, K., Miyatsuka, T., Katakami, N., and Matsuhisa, M.
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Journal Title
Adv. Drug Deliv. Rev
Volume: 61
Pages: 489-496
Related Report
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