Elucidation of the molecular mechanism of insulin resistance by investigating TBP-2/Txnip and chemical biology

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460386
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: MASUTANI Hiroshi 京都大学, ウイルス研究所, 准教授 (50252523)
• Co-Investigator(Renkei-kenkyūsha): FUJII Nobutaka 京都大学, 薬学研究科, 名誉教授 (60109014) ; OISHI Sinya 京都大学, 薬学研究科, 助教授 (80381739) ; ITOH Shinji 京都大学, 医学研究科, 助教 (50362512)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Txnip / 糖尿病 / 癌 / インスリン抵抗性 / 低分子化合物 / スクリーニング / ケミカルバイオロジー / 創薬

Outline of Final Research Achievements

Thioredoxin interacting protein (Txnip)/TBP-2 plays an important role in cancer suppression and glucose metabolism. To elucidate the molecular mechanism of Txnip, we performed proteomics analyses and identified interacting molecules with Txnip. This finding provides a basis for developing approaches to control diabetes and cancer. We also performed screening and identified low molecular weight compounds which suppress glucose-induced augmentation of Txnip expression, enhance glucose uptake and ameliorate high glucose in an animal model. Using these compounds, we revealed the regulatory pathway of Txnip expression. These results open the road to unveil the unknown signal transduction pathway and to develop novel drugs to control diabetes.

Free Research Field

病態生化学