Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 15, 2025; 16(6): 104973
Published online Jun 15, 2025. doi: 10.4239/wjd.v16.i6.104973
Ras homolog enriched in brain 1 regulates β cell mass and β cell function via mTORC1/AMPK/Notch1 pathways
Yan Yang, Wan-Juan Song, Jing-Jing Zhang
Yan Yang, Jing-Jing Zhang, National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
Wan-Juan Song, Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
Co-corresponding authors: Wan-Juan Song and Jing-Jing Zhang.
Author contributions: All authors contributed to the study conception and design; Yang Y were responsible for conceptualization, methodology, literature search, data collection, investigation, visualization, and original draft writing sections; Song WJ and Zhang JJ were responsible for supervision, and reviewed the article and made helpful suggestions; Song WJ and Zhang JJ contribute equally to this study as co-corresponding authors; all authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 82430029, No. 82330025, No. 82370807, and No. 82070807; Leading Talents Program of Hunan Province, No. 2022RC3078; and Natural Science Foundation of Hunan Province, China, No. 2021JJ30976.
Institutional review board statement: The use of isolated human islets was approved by the Ethics Committee of the Central South University Second Xiangya Hospital (No. MSRC2016 LF).
Institutional animal care and use committee statement: All procedures for animal use were in accordance with the Animal Care and Use Committee of the Second Xiangya Hospital Animal Care and Central South University (20240083).
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: sharing statement: All data supporting the findings of this study and unique biological materials used in this study are available from the corresponding authors upon reasonable request. Source data are provided with this paper.
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: Jing-Jing Zhang, MD, PhD, National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Renmin Middle Road, Changsha 410011, Hunan Province, China. doctorzhangjj@csu.edu.cn
Received: January 10, 2025
Revised: February 19, 2025
Accepted: April 3, 2025
Published online: June 15, 2025
Processing time: 157 Days and 1.7 Hours
Core Tip

Core Tip: Mechanisms underlying β cell dysfunction in diabetes remains unclear, our study explores the role of Ras homolog enriched in brain 1 (Rheb1) in regulating β-cell function and proliferation. The researchers found that Rheb1 is more highly expressed in islets from younger individuals (under 18) compared to adults. Rheb1 promotes β-cell proliferation through both the mTORC1 and AMP-activated protein kinase pathways, rather than relying solely on mTORC1. Moreover, Rheb1 also upregulated key transcription factor HNF4α in β cells. These findings suggest that Rheb1 plays a vital role in β-cell growth and function, making it a promising target for diabetes therapy.