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Downregulation of ALDH6A1 is a New Marker of Muscle Insulin Resistance in Type 2 Diabetes Mellitus

PURPOSE: Skeletal muscle insulin resistance (IR) is an important etiology of type 2 diabetes mellitus (T2DM); however, its molecular mechanism is yet to be fully defined. This study attempted to identify the gene expression patterns and molecular disorders in T2DM patients’ skeletal muscle samples....

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Autores principales: Liu, Song, Cai, Xiaojun, Wang, Tao, Xu, Jiwen, Cheng, Weilun, Wang, Xuling, Wei, Gangjie, Yan, Shuang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887615/
https://www.ncbi.nlm.nih.gov/pubmed/35241929
http://dx.doi.org/10.2147/IJGM.S343727
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author Liu, Song
Cai, Xiaojun
Wang, Tao
Xu, Jiwen
Cheng, Weilun
Wang, Xuling
Wei, Gangjie
Yan, Shuang
author_facet Liu, Song
Cai, Xiaojun
Wang, Tao
Xu, Jiwen
Cheng, Weilun
Wang, Xuling
Wei, Gangjie
Yan, Shuang
author_sort Liu, Song
collection PubMed
description PURPOSE: Skeletal muscle insulin resistance (IR) is an important etiology of type 2 diabetes mellitus (T2DM); however, its molecular mechanism is yet to be fully defined. This study attempted to identify the gene expression patterns and molecular disorders in T2DM patients’ skeletal muscle samples. METHODS: First, the difference in genetic expression among GSE25462 data was analyzed. Next, PPI network analysis of differential genes was carried out, after which the maladjustment module was identified. Then, an enrichment analysis and gene set enrichment analysis (GSEA) were carried out. Finally, the transcription factors that regulate the modular genes by raid were predicted. RESULTS: Most differentially expressed genes were found to be able to form an interaction network and cluster into 9 modules. These modular genes were shown to possess a significant correlation with immune inflammation and metabolic response. Importantly, the top 15 genes of area under receiver operating characteristic curve (AUC) were identified, and the expression of 10 genes by GSE12643, GSE18732 and GSE29221 was confirmed. The expression and AUC value of ALDH6A1 were then verified according to three sets of data, where ALDH6A1 was found to be negatively correlated with follicular helper T cells. However, among the predicted transcription regulators, HDAC was shown to have a better regulatory effect. CONCLUSION: The findings highlight that the dysregulation of ALDH6A1 expression in IR of T2DM may serve as a potential therapeutic target. ALDH6A1 is involved in the immune inflammation and metabolic pathways.
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spelling pubmed-88876152022-03-02 Downregulation of ALDH6A1 is a New Marker of Muscle Insulin Resistance in Type 2 Diabetes Mellitus Liu, Song Cai, Xiaojun Wang, Tao Xu, Jiwen Cheng, Weilun Wang, Xuling Wei, Gangjie Yan, Shuang Int J Gen Med Original Research PURPOSE: Skeletal muscle insulin resistance (IR) is an important etiology of type 2 diabetes mellitus (T2DM); however, its molecular mechanism is yet to be fully defined. This study attempted to identify the gene expression patterns and molecular disorders in T2DM patients’ skeletal muscle samples. METHODS: First, the difference in genetic expression among GSE25462 data was analyzed. Next, PPI network analysis of differential genes was carried out, after which the maladjustment module was identified. Then, an enrichment analysis and gene set enrichment analysis (GSEA) were carried out. Finally, the transcription factors that regulate the modular genes by raid were predicted. RESULTS: Most differentially expressed genes were found to be able to form an interaction network and cluster into 9 modules. These modular genes were shown to possess a significant correlation with immune inflammation and metabolic response. Importantly, the top 15 genes of area under receiver operating characteristic curve (AUC) were identified, and the expression of 10 genes by GSE12643, GSE18732 and GSE29221 was confirmed. The expression and AUC value of ALDH6A1 were then verified according to three sets of data, where ALDH6A1 was found to be negatively correlated with follicular helper T cells. However, among the predicted transcription regulators, HDAC was shown to have a better regulatory effect. CONCLUSION: The findings highlight that the dysregulation of ALDH6A1 expression in IR of T2DM may serve as a potential therapeutic target. ALDH6A1 is involved in the immune inflammation and metabolic pathways. Dove 2022-02-25 /pmc/articles/PMC8887615/ /pubmed/35241929 http://dx.doi.org/10.2147/IJGM.S343727 Text en © 2022 Liu et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Liu, Song
Cai, Xiaojun
Wang, Tao
Xu, Jiwen
Cheng, Weilun
Wang, Xuling
Wei, Gangjie
Yan, Shuang
Downregulation of ALDH6A1 is a New Marker of Muscle Insulin Resistance in Type 2 Diabetes Mellitus
title Downregulation of ALDH6A1 is a New Marker of Muscle Insulin Resistance in Type 2 Diabetes Mellitus
title_full Downregulation of ALDH6A1 is a New Marker of Muscle Insulin Resistance in Type 2 Diabetes Mellitus
title_fullStr Downregulation of ALDH6A1 is a New Marker of Muscle Insulin Resistance in Type 2 Diabetes Mellitus
title_full_unstemmed Downregulation of ALDH6A1 is a New Marker of Muscle Insulin Resistance in Type 2 Diabetes Mellitus
title_short Downregulation of ALDH6A1 is a New Marker of Muscle Insulin Resistance in Type 2 Diabetes Mellitus
title_sort downregulation of aldh6a1 is a new marker of muscle insulin resistance in type 2 diabetes mellitus
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887615/
https://www.ncbi.nlm.nih.gov/pubmed/35241929
http://dx.doi.org/10.2147/IJGM.S343727
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