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用于治疗代谢综合征的JAK抑制剂的最新进展。

Recent advances in JAK inhibitors for the treatment of metabolic syndrome.

作者信息

Collotta Debora, Franchina Maria Paola, Carlucci Virginia, Collino Massimo

机构信息

Department of Neuroscience "Rita Levi-Montalcini", University of Turin, Turin, Italy.

Chemsafe S.r.l., Turin, Italy.

出版信息

Front Pharmacol. 2023 Aug 24;14:1245535. doi: 10.3389/fphar.2023.1245535. eCollection 2023.


DOI:10.3389/fphar.2023.1245535
PMID:37701031
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10494544/
Abstract

With an epidemic spread, metabolic syndrome represents an increasingly emerging risk for the population globally, and is currently recognized as a pathological entity. It is represented by a cluster of different conditions including increased blood pressure, high blood sugar, excess body fat around the waist and abnormal cholesterol or triglyceride levels. These conditions lead directly to several disorders, including obesity, dyslipidemia, hyperglycaemia, insulin resistance, impaired glucose tolerance and hypertension causing an increase in cardiovascular risk and in particular atherosclerotic disease. Despite efforts to promote healthier lifestyles through exercise, reduced caloric intake, and improved dietary choices, the incidence and prevalence of metabolic syndrome continue to rise worldwide. Recent research has highlighted the involvement of signaling pathways in chronic inflammatory conditions like obesity and type 2 diabetes mellitus, revealing the significance of the JAK/STAT pathway in atherosclerotic events. This pathway serves as a rapid membrane-to-nucleus signaling module that regulates the expression of critical mediators. Consequently, JAK inhibitors (JAKi) have emerged as potential therapeutic options for metabolic diseases, offering a promising avenue for intervention. The aim of this review is to shed light on the emerging indications of JAK inhibitors in metabolic syndrome, emphasizing their potential role in attenuating associated inflammatory processes, improving insulin sensitivity, and addressing cross-talk with the insulin pathway, with the intention of contributing to efforts in the field of inflammation pharmacology.

摘要

随着疫情的蔓延,代谢综合征已成为全球人口中日益凸显的风险,目前被视为一种病理实体。它表现为一系列不同的状况,包括血压升高、血糖升高、腰部周围体脂过多以及胆固醇或甘油三酯水平异常。这些状况直接导致多种疾病,包括肥胖症、血脂异常、高血糖、胰岛素抵抗、糖耐量受损和高血压,从而增加心血管疾病风险,尤其是动脉粥样硬化疾病的风险。尽管人们努力通过运动、减少热量摄入和改善饮食选择来推广更健康的生活方式,但代谢综合征的发病率和患病率在全球范围内仍持续上升。最近的研究强调了信号通路在肥胖症和2型糖尿病等慢性炎症性疾病中的作用,揭示了JAK/STAT通路在动脉粥样硬化事件中的重要性。该通路作为一种快速的从细胞膜到细胞核的信号传导模块,调节关键介质的表达。因此,JAK抑制剂(JAKi)已成为代谢性疾病的潜在治疗选择,为干预提供了一条有前景的途径。本综述的目的是阐明JAK抑制剂在代谢综合征中的新适应症,强调其在减轻相关炎症过程、改善胰岛素敏感性以及解决与胰岛素通路的相互作用方面的潜在作用,以期为炎症药理学领域的研究做出贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16d0/10494544/744f9c6494f9/fphar-14-1245535-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16d0/10494544/ba4376be9810/fphar-14-1245535-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16d0/10494544/744f9c6494f9/fphar-14-1245535-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16d0/10494544/ba4376be9810/fphar-14-1245535-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16d0/10494544/744f9c6494f9/fphar-14-1245535-g002.jpg

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本文引用的文献

[1]
COVID-19 and the potential of Janus family kinase (JAK) pathway inhibition: A novel treatment strategy.

Front Med (Lausanne). 2022-8-30

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Pharmaceutics. 2022-5-6

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Front Med (Lausanne). 2021-7-9

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Eur J Pharmacol. 2021-7-5

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Ann Rheum Dis. 2021-7

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