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米非司酮治疗代谢综合征:超越库欣综合征

Mifepristone for Treatment of Metabolic Syndrome: Beyond Cushing's Syndrome.

作者信息

Díaz-Castro Francisco, Monsalves-Álvarez Matías, Rojo Leonel E, Del Campo Andrea, Troncoso Rodrigo

机构信息

Laboratorio de Investigación en Nutrición y Actividad Física (LABINAF), Instituto de Nutrición y Tecnología en Alimentos (INTA), Universidad de Chile, Santiago, Chile.

Advanced Center for Chronic Diseases (ACCDIS), Universidad de Chile, Santiago, Chile.

出版信息

Front Pharmacol. 2020 Apr 24;11:429. doi: 10.3389/fphar.2020.00429. eCollection 2020.

DOI:10.3389/fphar.2020.00429
PMID:32390830
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7193078/
Abstract

A growing body of research indicates that cortisol, the glucocorticoid product of the activation of the hypothalamic-pituitary-adrenal axis, plays a role in the pathophysiology of metabolic syndrome. In this regard, chronic exposure to cortisol is associated with risk factors related to metabolic syndrome like weight gain, type 2 diabetes, hypertension, among others. Mifepristone is the only FDA-approved drug with antiglucocorticoids properties for improved the glycemic control in patients with type 2 patients secondary to endogenous Cushing's syndrome. Mifepristone also have been shown positive effects in rodents models of diabetes and patients with obesity due to antipsychotic treatment. However, the underlying molecular mechanisms are not fully understood. In this perspective, we summarized the literature regarding the beneficial effects of mifepristone in metabolic syndrome from animal studies to clinical research. Also, we propose a potential mechanism for the beneficial effects in insulin sensitivity which involved the regulation of mitochondrial function in muscle cells.

摘要

越来越多的研究表明,下丘脑-垂体-肾上腺轴激活产生的糖皮质激素皮质醇在代谢综合征的病理生理学中起作用。在这方面,长期暴露于皮质醇与代谢综合征相关的危险因素有关,如体重增加、2型糖尿病、高血压等。米非司酮是唯一一种经美国食品药品监督管理局批准具有抗糖皮质激素特性的药物,可改善内源性库欣综合征继发的2型患者的血糖控制。米非司酮在糖尿病啮齿动物模型和因抗精神病药物治疗导致肥胖的患者中也显示出积极效果。然而,其潜在的分子机制尚未完全了解。从这个角度来看,我们总结了从动物研究到临床研究中关于米非司酮在代谢综合征中有益作用的文献。此外,我们提出了米非司酮对胰岛素敏感性产生有益作用的潜在机制,该机制涉及肌肉细胞中线粒体功能的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0035/7193078/d8f28884390b/fphar-11-00429-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0035/7193078/d8f28884390b/fphar-11-00429-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0035/7193078/d8f28884390b/fphar-11-00429-g001.jpg

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Mitochondrial dynamics in adaptive and maladaptive cellular stress responses.细胞应激反应中的适应性和失调性线粒体动态变化。
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Mifepristone enhances insulin-stimulated Akt phosphorylation and glucose uptake in skeletal muscle cells.米非司酮增强骨骼肌细胞中胰岛素刺激的 Akt 磷酸化和葡萄糖摄取。
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AMP-activated protein kinase, fatty acid metabolism, and insulin sensitivity.
米非司酮和雷帕霉素对交配雌性的寿命有非累加的益处。
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Conditional Inhibition of Eip75B Eliminates the Effects of Mating and Mifepristone on Lifespan in Female .条件性抑制 Eip75B 消除交配和米非司酮对雌性寿命的影响。
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Dhr96[1] mutation and maternal tudor[1] mutation increase life span and reduce the beneficial effects of mifepristone in mated female Drosophila.Dhr96[1] 突变和母性 tudor[1] 突变增加寿命并降低米非司酮在交配雌性果蝇中的有益作用。
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Medical treatment of Cushing's disease with concurrent diabetes mellitus.库欣病合并糖尿病的治疗。
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