Identification of a novel transcription factor that regulates diabetes-related hepatokine.

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K09740
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kanazawa University
• Principal Investigator: Misu Hirofumi 金沢大学, 医学系, 准教授 (80447680)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 2型糖尿病

Outline of Final Research Achievements

We reported that liver-derived secretory proteins SeP and LECT2 are proteins that induce insulin resistance and cause hyperglycemia. In this study, we establish a research base for developing a treatment for obesity type 2 diabetes. From the gene expression data in the liver of patients with type 2 diabetes, we were able to identify the transcription factor X that positively correlated with SeP and LECT2. Therefore, the liver-specific transcription factor X-deficient mouse was created. In these mice, the expression levels of transcription factor X and the expression levels of SeP and Lect2 were also decreased in the liver. Also, a decrease in gluconeogenic gene expression and a decrease in fasting blood glucose could be confirmed.

Free Research Field

代謝内分泌

Academic Significance and Societal Importance of the Research Achievements

肝臓は膨大な種類の分泌タンパクの産生源であり、血液凝固因子やアルブミンの産生を介して血液凝固状態の調整や血漿浸透圧の維持などの機能を発揮している。しかしながら肝臓はあまりに膨大な種類の分泌タンパクを産生していることから、これらの機能解析はこれまで十分に行われてこなかった。そこで、本研究では肝臓が未知の分泌タンパクを産生することで2型糖尿病における全身の病態形成に寄与していることを示すことができた。また、これらを制御する因子も発見できたことで、新たな肥満２型糖尿病に対する治療を開発するための研究基盤を確立することができた。