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核因子κB信号通路与2型糖尿病患者的二甲双胍耐药有关。

NF-kappa B signaling pathway is associated with metformin resistance in type 2 diabetes patients.

作者信息

Mansouri Vahid, Bandarian Fatemeh, Razi Farideh, Razzaghi Zahra, Rezaei-Tavirani Majid, Rezaei Mitra, Arjmand Babak, Rezaei-Tavirani Mostafa

机构信息

Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Diabetes Metab Disord. 2024 Jul 6;23(2):2021-2030. doi: 10.1007/s40200-024-01458-8. eCollection 2024 Dec.

Abstract

INTRODUCTION

Metformin is an essential medicine that is most widely prescribed frontline for the treatment of Type 2 diabetes (T2D). Metformin upgraded glycemic control in T2D patients without hypoglycemic effects in patients. This assessment aims to understand molecular mechanism mechanisms in non-responder patients to metformin.

METHODS

Gene expression profiles of responder and non-responder T2D patients to metformin are extracted from Gene Expression Omnibus (GEO) and are evaluated by the GEO2R program to find the significant differentially expressed genes (DEGs). The significant DEGs have been studied via action map gene ontology analyses.

RESULTS

Results indicate that 563 significant DEGs discriminate non-responders from responder groups. "NF-kappa B signaling pathway" and 11 DEGs including BIRC3, CCL4L2, CXCL2, ICAM1, LYN, MYD88, RELA, SYK, TLR4, TNFAIP3, and TRIM25 were pointed out as core of drug resistance.

CONCLUSION

It can be concluded that there are differences between gene expression analysis, the response of diabetic patients to metformin. Results indicate that dysregulation of the "NF-kappa B signaling pathway" and TNFAIP3, BIRC3, RELA, MYD88, TLR4, and ICAM1 is associated with drug resistance in T2D patients.

摘要

引言

二甲双胍是治疗2型糖尿病(T2D)最广泛处方的一线基本药物。二甲双胍可改善T2D患者的血糖控制,且不会使患者出现低血糖效应。本评估旨在了解二甲双胍无反应患者的分子机制。

方法

从基因表达综合数据库(GEO)中提取二甲双胍反应者和无反应者T2D患者的基因表达谱,并通过GEO2R程序进行评估,以找出显著差异表达基因(DEG)。通过作用图谱基因本体分析对显著的DEG进行了研究。

结果

结果表明,563个显著的DEG可区分无反应者和反应者组。“NF-κB信号通路”以及包括BIRC3、CCL4L2、CXCL2、ICAM1、LYN、MYD88、RELA、SYK、TLR4、TNFAIP3和TRIM25在内的11个DEG被指出是耐药性的核心。

结论

可以得出结论,糖尿病患者对二甲双胍的反应在基因表达分析方面存在差异。结果表明,“NF-κB信号通路”以及TNFAIP3、BIRC3、RELA、MYD88、TLR4和ICAM1的失调与T2D患者的耐药性有关。

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