Perturbation of redox balance in pathophysiology of diabetes

2021 Fiscal Year Final Research Report

• Project/Area Number: 17H04199
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kanazawa University
• Principal Investigator: Takamura Toshinari 金沢大学, 医学系, 教授 (00324111)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: 2型糖尿病 / ヘパトカイン / 酸化ストレス / 還元ストレス / 活性酸素種 / 熱産生 / 褐色脂肪組織 / 骨粗鬆症

Outline of Final Research Achievements

Various antioxidant drugs have been clinically applied to reduce oxidative stress, but none have achieved sufficient therapeutic efficacy. Selenoprotein P (SeP) is a hepatokine, a bioactive molecule derived from the liver, which plays roles in the pathogenesis of type 2 diabetes. In the present study, we show that SeP is an endogenous factor that induces signal transduction via eliminating physiological reactive oxygen species. Such SeP-mediated reductive stress caused diabetic pathology in the brown adipose tissue and bone. These findings suggest that SeP is a potential novel therapeutic target against diabetic complications.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究はSePが還元ストレスを介して、臓器におけるシグナル伝達抵抗性をもたらすことを明らかにした。よって、糖尿病、肥満症、動脈硬化症をはじめとする生活習慣病に対して、新しい概念に基づく治療・診断技術開発、そして治療薬への道が拓ける。さらに学術的にも、これまで酸化ストレスによって説明されてきたインスリン抵抗性や老化のメカニズムに、「制御された生理的ROSの機能」の視点から再構築を迫ることになる。