Direct intervention of incretin to protect the blood-retinal barrier - Suppression on onset and progression of diabetic retinopathy -

2015 Fiscal Year Final Research Report

• 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
• 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

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.

Free Research Field

病態生化学