Quercetin Alleviates Ferroptosis of Pancreatic β Cells in Type 2 Diabetes.
Quercetin Alleviates Ferroptosis of Pancreatic β Cells in Type 2 Diabetes.
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DOI：
10.3390/nu12102954
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发表时间：
2020-09-27
期刊：
影响因子：
5.9
通讯作者：
Yao P
中科院分区：
文献类型：
--
作者：
Li D;Jiang C;Mei G;Zhao Y;Chen L;Liu J;Tang Y;Gao C;Yao P
(1)背景：胰腺铁沉积在2型糖尿病（T2DM）的进展中被发现；然而，铁下沉是否导致胰腺β细胞（PBC）功能障碍仍然是一个谜。此外，槲皮素的潜在保护作用也难以捉摸；(2)方法：采用低剂量STZ多次注射建立T2DM小鼠模型，随后给予槲皮素干预4个月；(3)结果：与T2DM对照组相比，糖耐量、糖尿病症状、胰岛素抵抗稳态模型评估（HOMA- ir）和β细胞稳态模型评估（HOMA-β）指数基本正常化。T2DM小鼠胰岛扭曲，特别是PBC线粒体萎缩，嵴丢失，槲皮素可改善这种情况。同时，槲皮素降低了2型糖尿病小鼠胰岛的铁水平。尽管有代偿性的xCT上调，T2DM模制仍导致谷胱甘肽（GSH）减少，谷胱甘肽过氧化物酶4 （GPX4）下调，并诱导胰腺组织氧化应激，槲皮素可部分消除这种氧化应激。更重要的是，凋亡诱导的erastin或ras选择性致死化合物3 （RSL-3）使胰岛素分泌恶化。槲皮素、铁下垂抑制剂他汀-1和铁螯合去铁胺在高糖刺激下恢复细胞活力；(4)结论：我们的研究结果表明，铁下垂导致PBC丢失和功能障碍。槲皮素通过抑制胰腺铁沉积和PBC铁下垂对T2DM有潜在的有益作用，强调了槲皮素控制T2DM的有前景的策略。
(1) Background: Pancreatic iron deposition has been found in the progression of type 2 diabetes (T2DM); however, whether ferroptosis contributes to the dysfunction of pancreatic β cells (PBC) remains enigmatic. Moreover, the potential protective effect of quercetin is also elusive; (2) Methods: T2DM mice model was established by multiple low dose streptozocin (STZ) injection, after which quercetin was intervened for 4 months; (3) Results: Substantially normalized glucose tolerance, diabetic symptoms, homeostasis model assessment for insulin resistance (HOMA-IR), and homeostasis model assessment for β cell (HOMA-β) index in comparison with the findings of T2DM control. Distorted pancreatic islets and especially shrunken mitochondria with cristae loss in PBC were observed in T2DM mice, which was ameliorated by quercetin. Meanwhile, quercetin lowered the iron level particularly in the islet in T2DM mice. In spite of compensatory xCT up-regulation, T2DM molding depleted glutathione (GSH), down-regulated glutathione peroxidase 4 (GPX4), and induced oxidative stress in pancreatic tissue, which was abolished partially by quercetin. More importantly, insulin secretion was worsened by ferroptosis-inducing erastin or RAS-selective lethal compounds 3 (RSL-3). Quercetin, ferroptosis inhibitor ferrostatin-1 and iron-chelating deferoxamine, rescued cell viability when cells were challenged with high-glucose; (4) Conclusions: Our findings identify that ferroptosis contributes to the PBC loss and dysfunction. Quercetin exerts beneficial effects on T2DM potentially by inhibiting pancreatic iron deposition and PBC ferroptosis, highlighting promising control strategies of T2DM by quercetin.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
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影响因子：
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影响因子：
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作者：
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影响因子：
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