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2019 Fiscal Year Final Research Report

Augmentation in insulin resistance by pyrethroid pesticide invalidating the claim of its safety

Research Project

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Project/Area Number 17K09154
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hygiene and public health
Research InstitutionUniversity of Toyama

Principal Investigator

Cui Zheng-Guo  富山大学, 学術研究部医学系, 助教 (90572115)

Co-Investigator(Kenkyū-buntansha) 稲寺 秀邦  富山大学, 学術研究部医学系, 教授 (10301144)
小川 良平  富山大学, 学術研究部医学系, 准教授 (60334736)
Project Period (FY) 2017-04-01 – 2020-03-31
Keywordsフェンバレレート / がん / 糖代謝
Outline of Final Research Achievements

Fenvalerate (Fen) is a synthetic pyrethroid insecticide and a known environmental endocrine disruptor. Previous studies reported that pyrethroid exposure could increase the risk of diabetes. On the other hand, Fen is able to decrease mouse serum glucose, the complicate mechanism is largely unknown. Here we found that Fen promoted ATP generation, lactate production, and glucose uptake, which were similar to the Warburg effect. Moreover, Fen enhanced insulin receptor sensitivity and endocytosis by PI3K-AKT pathway. Fen sustained the Warburg effect dependent on the generation of reactive oxygen species. Potent antioxidants N-acetyl Cysteine and ascorbic acid inhibited the Warburg effect induced by Fen. Finally, chronic Fen exposure fortified HepG2 cells against metformin-induced cell death. In conclusion, Fen enabled hepatoma cells to adapt for their ambient environment.

Free Research Field

公衆衛生学

Academic Significance and Societal Importance of the Research Achievements

ピレスロイド系農薬は家庭用あるいは果実や野菜の農業生産用に広く利用される殺虫剤である。実験動物等において神経系や生殖ホルモン系統への悪影響が報告されているが、糖代謝に及ぼす影響については不明な点が多い。本研究は、フェンバレレートの曝露ががん細胞の糖代謝に影響を及ぼすことによりワールブルク効果に類した現象を引き起こし、抗がん剤における細胞死の抵抗性を誘発することを見出し、さらにその分子メカニズムの一部を解明した。それは、ピレスロイド系農薬を使用する農業従事者の健康を守るために重要な情報を提供することと考えられる。

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Published: 2021-02-19  

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