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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 15, 2025; 16(11): 112236
Published online Nov 15, 2025. doi: 10.4239/wjd.v16.i11.112236
Published online Nov 15, 2025. doi: 10.4239/wjd.v16.i11.112236
Androgen receptor mutations in familial androgen insensitivity syndrome: A metabolic reprogramming pathway to type 2 diabetes susceptibility
Cheng Luo, Liang-Yan Hua, Cheng-Zheng Duan, Shi-Yu Xu, Department of Endocrinology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou 324000, Zhejiang Province, China
Wei-Wei Zhang, Department of Science and Education, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou 324000, Zhejiang Province, China
Mei-Qi Zeng, Department of Ophthalmology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou 324000, Zhejiang Province, China
Hui Xu, Department of Hospital Management, Quzhou Hospital of Traditional Chinese Medicine, Quzhou 324000, Zhejiang Province, China
Shuo Zhan, Department of Endocrinology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Xiao-Fei Pan, School of Clinical Medical, Hangzhou Medical College, Hangzhou 311300, Zhejiang Province, China
Da Sun, Institute of Life Sciences and Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325000, Zhejiang Province, China
Li-Ya Ye, Department of Gynecology, The Second People’s Hospital of Quzhou, Quzhou 324002, Zhejiang Province, China
Dong-Juan He, Department of Endocrinology, The Second People’s Hospital of Quzhou, Quzhou 324002, Zhejiang Province, China
Co-first authors: Cheng Luo and Wei-Wei Zhang.
Co-corresponding authors: Li-Ya Ye and Dong-Juan He.
Author contributions: Luo C and Zhang WW were responsible for the conceptualization, writing of the original draft, literature review and summary, they contributed equally to this article, they are the co-first authors of this manuscript; Hua LY and Zeng MQ undertook formal analysis and data validation; Xu SY and Duan CZ were in charge of methodology and investigation; Xu H and Zhan S handled supervision and project administration; Pan XF and Sun D took on literature review and figure preparation; Ye LY and He DJ played important and integral roles in the study design and manuscript preparation, including supervising the study design, providing critical revisions, and ensuring the integrity of the research findings; they contributed equally to this article, they are the co-corresponding authors of this manuscript; and all authors thoroughly reviewed and endorsed the final manuscript.
Supported by the Quzhou Science and Technology Plan Project, No. 2022K69.
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: Dong-Juan He, MD, Chief Physician, Dean, Director, Professor, Department of Endocrinology, The Second People’s Hospital of Quzhou, No. 338 Xin’an Avenue, Qujiang District, Quzhou 324002, Zhejiang Province, China.
Received: July 22, 2025
Revised: August 6, 2025
Accepted: September 22, 2025
Published online: November 15, 2025
Processing time: 116 Days and 0.2 Hours
Revised: August 6, 2025
Accepted: September 22, 2025
Published online: November 15, 2025
Processing time: 116 Days and 0.2 Hours
Core Tip
Core Tip: Familial androgen insensitivity syndrome (AIS), caused by androgen receptor gene mutations, has long been viewed as a disorder of sex development. However, recent findings revealed that androgen receptor dysfunction also drives metabolic reprogramming in key tissues - pancreatic β-cells, skeletal muscle, liver, and adipose tissue - leading to insulin resistance and increased susceptibility to type 2 diabetes mellitus. This article highlights emerging evidence of glucagon-like peptide-1 signaling disruption, mitochondrial dysfunction, and inflammatory imbalance in AIS. We propose an integrated framework of genetic screening, endocrine surveillance, and individualized therapy to improve long-term metabolic outcomes and prevent cardiometabolic complications in AIS patients.