Project/Area Number |
25460654
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Applied pharmacology
|
Research Institution | Gifu Pharmaceutical University |
Principal Investigator |
ADACHI TETSUO 岐阜薬科大学, 薬学部, 教授 (40137063)
|
Co-Investigator(Kenkyū-buntansha) |
HARA Hirokazu 岐阜薬科大学, 薬学部, 准教授 (30305495)
KAMIYA Tetsuro 岐阜薬科大学, 薬学部, 助教 (60453057)
|
Co-Investigator(Renkei-kenkyūsha) |
IKEDA Tsunehiko 大阪医科大学, 医学部, 教授 (70222891)
|
Research Collaborator |
YASUDA Hiroyuki
MAKINO Junya
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 糖尿病 / エピジェネティクス / ストレス / インクレチン / 抗酸化酵素 / 血管内皮細胞 / シグナル伝達 |
Outline of Final Research Achievements |
Exendin-4 is an analog of the glucagon-like peptide 1 (GLP-1) and is used in the treatment of type 2 diabetes. Since human GLP-1 receptor has been identified in various cells besides pancreatic cells, exendin-4 is expected to exert extrapancreatic actions. The expression of extracellular-superoxide dismutase (EC-SOD), a major SOD isozyme that is crucially involved in redox homeostasis, is regulated by epigenetic factors. We demonstrated that exendin-4 induced the expression of EC-SOD in A549 human lung adenocarcinoma epithelial cell line and human retinal microvascular endothelial cells through demethylation of some methyl-CpG sites and histone H3 acetylation at the EC-SOD proximal promoter region, respectively. Moreover, plasma EC-SOD concentrations in diabetic patients were elevated by incretin-based therapies. Therefore, incretin-based therapies may exert direct extrapancreatic effects in order to protect blood vessels by enhancing anti-oxidative activity.
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