阿那白素通过下调Th17反应改善妊娠糖尿病小鼠模型中的胰岛素抵抗和炎症

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-10-10 DOI:10.1016/j.cyto.2025.157039

Lingyan Zhang , Fudan Huang , Shaik Althaf Hussain , Yi Tian

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引用次数: 0

摘要

妊娠期糖尿病（GDM）与低度炎症相关，可导致胰岛素抵抗和糖代谢失调。Anakinra是IL-1受体拮抗剂（IL-1Ra）的重组形式，在控制几种炎症性疾病方面显示出希望。本研究旨在评估阿那白在GDM遗传模型中控制炎症和糖代谢的潜力。以妊娠C57BL/KsJdb/+ (db/+)小鼠为GDM小鼠模型，观察其糖代谢、胰岛素抵抗及炎症介质水平。同时还分析了小鼠脾脏中Th17和Treg细胞的数量。在后代中研究了一些gdm相关参数，并对肝脏和胎盘的氧化应激进行了评估。阿那白改善了GDM小鼠的葡萄糖耐量和胰岛素敏感性，控制了妊娠小鼠的体重增加。在anakinra小鼠中，作为炎症过程关键介质的Th17细胞数量下降，血清中促炎细胞因子水平以及NF-κB通路的激活也相应下降。此外，在anakinra处理的小鼠中，t细胞向胎盘的浸润减少。Anakinra通过靶向低度炎症和改善葡萄糖代谢，证明了控制GDM的潜力。考虑到小分子的公平性质使其成为合适的治疗工具，Anakinra可能是更有效控制GDM的候选治疗药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Anakinra ameliorates insulin resistance and inflammation in a murine model of gestational diabetes through downregulation of Th17 responses Anakinra for the treatment of GDM in mice

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Anakinra ameliorates insulin resistance and inflammation in a murine model of gestational diabetes through downregulation of Th17 responses Anakinra for the treatment of GDM in mice

Gestational diabetes mellitus (GDM) is associated with low-grade inflammation which can contribute to insulin resistance and dysregulated glucose metabolism. Anakinra is a recombinant form of IL-1 receptor antagonist (IL-1Ra) that has shown promise in the control of several inflammatory diseases. The present study aimed to evaluate the potential of Anakinra in the control of inflammation and glucose metabolism in a genetic model of GDM.

Pregnant C57BL/KsJdb/+ (db/+) mice were used as the murine model of GDM and the glucose metabolism, insulin resistance as well as levels of inflammatory mediators were evaluated. The populations of Th17 and Treg cells were also analyzed in spleens of mice. Some GDM-associated parameters were studied in offspring along with an evaluation of oxidative stress in the liver and placenta.

Anakinra improved the glucose tolerance and insulin sensitivity of GDM mice and controlled the weight gain of the pregnant mice. The population of Th17 cells as key mediators of inflammatory processes declined in the Anakinra-received mice and the serum levels of pro-inflammatory cytokines as well as the activation of the NF-κB pathway declined accordingly. Besides, the infiltration of T-cells into the placenta was diminished in Anakinra-treated mice.

Anakinra demonstrated a potential for control of GDM by targeting low-grade inflammation and improving glucose metabolism. Regarding the fair properties of small molecules that render them suitable therapeutic tools, Anakinra might be a candidate therapeutic for the control of GDM more efficiently.

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.