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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Sep 15, 2025; 16(9): 109274
Published online Sep 15, 2025. doi: 10.4239/wjd.v16.i9.109274
Published online Sep 15, 2025. doi: 10.4239/wjd.v16.i9.109274
β-cell dedifferentiation in type 2 diabetes: Interplay of metabolic stress, endoplasmic reticulum dysfunction, and forkhead box protein O1 inhibition
Ashraf Al Madhoun, Department of Translational Medicine, Dasman Diabetes Institute, Dasman 15400, Kuwait
Fatemah Bahman, Rasheed Ahmad, Department of Immunology and Microbiology, Dasman Diabetes Institute, Dasman 15400, Kuwait
Author contributions: Al Madhoun A designed the study, wrote and edited the manuscript; Bahman F and Ahmad R reviewed the literature and revised the manuscript. All authors approved the final version manuscript.
Supported by Kuwait Foundation for the Advancement of Sciences, No. RACB-2021-007.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ashraf Al Madhoun, PhD, Senior Scientist, Department of Translational Medicine, Dasman Diabetes Institute, Jassim AlBahar Street, Dasman 15400, Kuwait.
Received: May 7, 2025
Revised: June 2, 2025
Accepted: July 31, 2025
Published online: September 15, 2025
Processing time: 128 Days and 5.2 Hours
Revised: June 2, 2025
Accepted: July 31, 2025
Published online: September 15, 2025
Processing time: 128 Days and 5.2 Hours
Core Tip
Core Tip: This editorial highlights the emerging role of β-cell dedifferentiation as a central mechanism of β-cell failure in type 2 diabetes, alongside apoptosis. We emphasize recent findings that chronic metabolic stressors, namely glucotoxicity and lipotoxicity, initiate ER stress and suppress forkhead box protein O1 activity, leading to the loss of β-cell identity and function. The reversibility of this process introduces new therapeutic possibilities aimed at preserving or restoring en