Comprehensive analysis of endoplasmic reticulum stress-related mechanisms in type 2 diabetes mellitus

doi:10.4239/wjd.v14.i6.820

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World Journal of Diabetes

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1948-9358

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World J Diabetes. Jun 15, 2023; 14(6): 820-845
Published online Jun 15, 2023. doi: 10.4239/wjd.v14.i6.820

Comprehensive analysis of endoplasmic reticulum stress-related mechanisms in type 2 diabetes mellitus

Bo Liang, Shu-Wen Chen, Yuan-Yuan Li, Shun-Xiao Zhang, Yan Zhang

Bo Liang, Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, China

Shu-Wen Chen, Yuan-Yuan Li, Shun-Xiao Zhang, Yan Zhang, Department of Endocrinology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200000, China

Author contributions: Liang B and Zhang Y conceived, designed, and planned the study; Liang B, Chen SW, and Li YY analyzed the data; Liang B, Chen SW, and Zhang SX interpreted the data; Liang B drafted the manuscript; Zhang Y revised the manuscript; All authors collected the data, they all read and approved the final manuscript.

Institutional review board statement: The research does not involve ethics and animal experiments.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Data sharing statement: Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE166502andGPL10558.

Corresponding author: Yan Zhang, MD, PhD, Academic Editor, Professor, Department of Endocrinology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, No. 181 Youyi Road, Baoshan District, Shanghai 200000, China. yan_2999bs@163.com

Received: December 10, 2022
Peer-review started: December 10, 2022
First decision: December 26, 2022
Revised: December 27, 2022
Accepted: April 4, 2023
Article in press: April 4, 2023
Published online: June 15, 2023
Processing time: 186 Days and 22.5 Hours

Abstract

BACKGROUND

The endoplasmic reticulum (ER) is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health. Type 2 diabetes mellitus (T2DM) is a serious threat to human health, but the ER stress (ERS)-related mechanisms in T2DM have not been fully elucidated.

AIM

To identify potential ERS-related mechanisms and crucial biomarkers in T2DM.

METHODS

We conducted gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) in myoblast and myotube form GSE166502, and obtained the differentially expressed genes (DEGs). After intersecting with ERS-related genes, we obtained ERS-related DEGs. Finally, functional analyses, immune infiltration, and several networks were established.

RESULTS

Through GSEA and GSVA, we identified several metabolic and immune-related pathways. We obtained 227 ERS-related DEGs and constructed several important networks that help to understand the mechanisms and treatment of T2DM. Finally, memory CD4⁺ T cells accounted for the largest proportion of immune cells.

CONCLUSION

This study revealed ERS-related mechanisms in T2DM, which might contribute to new ideas and insights into the mechanisms and treatment of T2DM.

Keywords: Endoplasmic reticulum stress; Type 2 diabetes mellitus; Biomarkers; Memory CD4⁺ T cells

Core Tip: This study revealed endoplasmic reticulum stress-related mechanisms in type 2 diabetes mellitus (T2DM), which might contribute to new ideas and insights for the mechanisms and treatment of T2DM.