Peng Y, Zhang DD, Gan L, Zhang JQ. Targeting Ras homolog enriched in brain 1 to restore β-cell mass and function: A potential therapeutic strategy for diabetes. World J Diabetes 2025; 16(9): 109768 [DOI: 10.4239/wjd.v16.i9.109768]
Corresponding Author of This Article
Jia-Qi Zhang, MD, PhD, Associate Professor, Department of Ultrasound Imaging, Postgraduate Union Training Base of Xiangyang No. 1 People’s Hospital, School of Medicine, Wuhan University of Science and Technology, No. 15 Jiefang Road, Fancheng District, Xiangyang 441000, Hubei Province, China. 347235272@qq.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Sep 15, 2025; 16(9): 109768 Published online Sep 15, 2025. doi: 10.4239/wjd.v16.i9.109768
Targeting Ras homolog enriched in brain 1 to restore β-cell mass and function: A potential therapeutic strategy for diabetes
Yao Peng, Dong-Dong Zhang, Ling Gan, Jia-Qi Zhang
Yao Peng, Ling Gan, Jia-Qi Zhang, Department of Ultrasound Imaging, Postgraduate Union Training Base of Xiangyang No. 1 People’s Hospital, School of Medicine, Wuhan University of Science and Technology, Xiangyang 441000, Hubei Province, China
Dong-Dong Zhang, Department of Oncology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang 441100, Hubei Province, China
Co-first authors: Yao Peng and Dong-Dong Zhang.
Co-corresponding authors: Ling Gan and Jia-Qi Zhang.
Author contributions: Peng Y and Zhang DD made equal contributions as co-first authors; Zhang JQ contributed to the writing and editing of the manuscript; Peng Y contributed to the discussion and design of the manuscript; Zhang DD contributed to the literature search; Gan L designed the overall concept and outline of the manuscript; Gan L and Zhang JQ made equal contributions as co-corresponding authors. All authors have read and approve the final manuscript.
Supported by Hubei Provincial Natural Science Foundation, No. 2025AFB845; and Graduate Innovation and Entrepreneurship Fund of Wuhan University of Science and Technology, No. JCX2024044.
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: Jia-Qi Zhang, MD, PhD, Associate Professor, Department of Ultrasound Imaging, Postgraduate Union Training Base of Xiangyang No. 1 People’s Hospital, School of Medicine, Wuhan University of Science and Technology, No. 15 Jiefang Road, Fancheng District, Xiangyang 441000, Hubei Province, China. 347235272@qq.com
Received: May 21, 2025 Revised: June 14, 2025 Accepted: August 6, 2025 Published online: September 15, 2025 Processing time: 113 Days and 18.5 Hours
Abstract
This editorial highlighted the central role of pancreatic β-cell dysfunction in the pathogenesis of diabetes mellitus and discussed the emerging significance of Ras homolog enriched in brain 1 (Rheb1) as a key regulator of β-cell mass and insulin-secretory capacity. While molecular mechanisms governing β-cell homeostasis remain incompletely defined, Yang et al have recently demonstrated that Rheb1 could promote β-cell proliferation through dual activation of mechanistic target of rapamycin complex 1 and AMP-activated protein kinase signaling pathways, rather than relying solely on mechanistic target of rapamycin complex 1. Notably, Rheb1 expression is higher in pancreatic islets from younger individuals and upregulates hepatocyte nuclear factor 4 alpha, which is recognized as a transcription factor essential for β-cell identity and insulin production. These insights position Rheb1 as a pivotal regulator of β-cell growth and metabolic function, with potential therapeutic implications for diabetes. Targeting Rheb1 may shift treatment paradigms from conventional glucose-lowering strategies toward β-cell restoration, providing a novel approach to preserve or enhance functional β-cell mass in diabetic patients. Further investigation into Rheb1’s upstream regulators and downstream effectors may provide innovative therapeutic directions.
Core Tip: Dysregulation of β-cell mass and function contributes to the development and progression of diabetes mellitus. In a recent study, Yang et al identified Ras homolog enriched in brain 1 (Rheb1) as a critical regulator of β-cell proliferation via both mechanistic target of rapamycin complex 1 and AMP-activated protein kinase signaling pathways. Rheb1 also enhances hepatocyte nuclear factor 4 alpha expression, further supporting its role in maintaining β-cell functionality. These results reveal an intricate signaling network through by Rheb1 supports β-cell growth and survival, highlighting its potential as a therapeutic target for diabetes management. Further research is warranted to explore the translational applications of these findings.
