Development of PI Polyamide targeting adiponectin gene

Research Project

Project/Area Number	25461092
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Cardiovascular medicine
Research Institution	Nihon University
Principal Investigator	TSUNEMI Akiko 日本大学, 医学部, 研究員 (90646035)
Co-Investigator(Kenkyū-buntansha)	UENO Takahiro 日本大学, 医学部, 兼任講師 (40386008)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	PI ポリアミド / アディポネクチン / PIポリアミド / メタボリックシンドローム / 抗動脈硬化作用
Outline of Final Research Achievements	Pyrrole-Imidazole polyamides (PI polyamides) are new chemical compounds that specifically inhibit transcription factor binding. A PI polyamide that targets mouse adiponectin(APN) and increases APN gene expression was designed. Treatment of 3T3-L1 cells with 1.0μM PI polyamide significantly increased APN mRNA expression. PI polyamide administration significantly improved blood glucose level during the glucose tolerance test in db/db mouse. PI polyamide treatment also improved insulin sensitivity in db/db mouse evaluated by the insulin loading test. PI polyamide significantly decreased plasma triglyceride and free fatty acid levels in db/db mouse. Moreover, lipid deposits of the liver in db/db mouse were decreased by PI polyamide administration.The designed PI polyamide targeting SPN gene successfully increased APN expression, and improved insulin sensitivity in the diabetic mouse model. This novel compound is promising as a useful compound in the treatment of diabetes.