NRF2 缺乏导致在怀孕期间和妊娠期糖尿病期间β细胞适应不充分
Fatema Haidery1, Luca Lambertini1, Isabelle Tse1
1Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Redox biology
|March 7, 2025
概括
核因子NRF2对于在怀孕期间保持健康的胰腺β细胞功能至关重要. 它通过雌激醇的激活可以防止氧化应激,这表明NRF2是孕期糖尿病 (GDM) 的潜在治疗标.
科学领域:
- 内分泌学 在内分泌学.
- 代谢疾病 代谢疾病
- 生殖生物学 生殖生物学
背景情况:
- 由于胎儿的葡萄糖需求,怀孕会增加母亲的胰岛素抵抗.
- 母性胰腺β细胞质量适应地扩大,以维持血糖平衡.
- 贝塔细胞适应的缺陷可能导致妊娠期糖尿病 (GDM),与氧化应激有关.
研究的目的:
- 调查NRF2在怀孕期间β细胞适应中的作用.
- 探索NRF2,氧化应激和妊娠糖尿病 (GDM) 之间的联系.
主要方法:
- 使用可诱导β细胞特异性Nrf2删除 (βNrf2KO) 的小鼠模型.
- 评估了β细胞的增殖,氧化应激,脂质过氧化和细胞死亡.
- 研究了17-β-雌二醇 (E2) 对NRF2水平和β细胞保护的影响.
主要成果:
- 在怀孕晚期 (GD15) 的小鼠β细胞中,NRF2水平上调.
- βNrf2KO小鼠显示β细胞扩张受损,氧化应激增加,葡萄糖平衡受损.
- 17-β-雌二醇 (E2) 增加了NRF2水平,NRF2下调阻断了E2对氧化应激的保护作用.
结论:
- 在怀孕期间,NRF2在胰腺β细胞中调节氧化应激起着至关重要的作用.
- 妊娠激素E2通过NRF2激活来保护β细胞.
- NRF2被确定为预防和治疗GDM的潜在治疗标.
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