...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell metabolism >The furan fatty acid metabolite CMPF is elevated in diabetes and induces β cell dysfunction
【24h】

The furan fatty acid metabolite CMPF is elevated in diabetes and induces β cell dysfunction

机译：呋喃脂肪酸代谢产物CMPF在糖尿病中升高，并诱发β细胞功能障碍

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Gestational diabetes (GDM) results from failure of the β cells to adapt to increased metabolic demands; however, the cause of GDM and the extremely high rate of progression to type 2 diabetes (T2D) remains unknown. Using metabolomics, we show that the furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is elevated in the plasma of humans with GDM, as well as impaired glucose-tolerant and T2D patients. In mice, diabetic levels of plasma CMPF induced glucose intolerance, impaired glucose-stimulated insulin secretion, and decreased glucose utilization. Mechanistically, we show that CMPF acts directly on the β cell, causing impaired mitochondrial function, decreasing glucose-induced ATP accumulation, and inducing oxidative stress, resulting in dysregulation of key transcription factors and ultimately reduced insulin biosynthesis. Importantly, specifically blocking its transport through OAT3 or antioxidant treatment could prevent CMPF-induced β cell dysfunction. Thus, CMPF provides a link between β cell dysfunction and GDM/T2D that could be targeted therapeutically.
机译：β细胞无法适应新陈代谢的需求导致妊娠糖尿病（GDM）。然而，GDM的病因和发展为2型糖尿病（T2D）的极高发生率仍然未知。使用代谢组学，我们显示呋喃脂肪酸代谢物3-羧基-4-甲基-5-丙基-2-呋喃丙酸（CMPF）在患有GDM的人的血浆中以及糖耐量低和T2D患者中升高。在小鼠中，血浆CMPF的糖尿病水平引起葡萄糖耐受不良，葡萄糖刺激的胰岛素分泌受损以及葡萄糖利用率降低。从机理上讲，我们表明CMPF直接作用于β细胞，导致线粒体功能受损，降低了葡萄糖诱导的ATP积累，并诱导了氧化应激，从而导致关键转录因子的调节失调，最终降低了胰岛素的生物合成。重要的是，通过OAT3或抗氧化剂处理专门阻断其运输可以预防CMPF诱导的β细胞功能障碍。因此，CMPF提供了β细胞功能障碍与GDM / T2D之间的联系，而这种联系可以进行治疗。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号