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World J Diabetes. Nov 15, 2026; 17(11): 121630
Published online Nov 15, 2026. doi: 10.4239/wjd.121630
Published online Nov 15, 2026. doi: 10.4239/wjd.121630
Postmenopausal high-gonadotropin-releasing hormone environment mediates pancreatic β-cell compensation via the cAMP-PKA-PDX1 pathway
Xue-Juan Dai, Lu Yang, Chu-Chu Kong, Cui-Ying Ye, Zi-Xuan Xu, Ya-Xin Hu, Wei Wang, Department of Endocrinology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China
Shi-Cong Gao, Department of Gastrointestinal Surgery, Xiang’an Hospital of Xiamen Uni
Peng-Tao Chen, Cheng-Yong He, Zheng-Hong Zuo, State Key Laboratory of Cellular Stress Biology, Department of Endocrinology, Xiang’an Hospital of Xiamen University, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, Fujian Province, China
Co-corresponding authors: Zheng-Hong Zuo and Wei Wang.
Author contributions: Dai XJ performed the majority of the experiments, analyzed the data, and wrote the original draft; Gao SC assisted with the animal model construction; Ye CY, Xu ZX, and Hu YX contributed to the cell culture and molecular biology assays; Chen PT, Yang L, and Kong CC assisted with animal husbandry and sample collection; He CY, Zuo ZH, and Wang W supervised the project, acquired funding, and reviewed and edited the manuscript, who is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis; Wang W and Zuo ZH contributed equally as co-corresponding authors. All authors have read and approved the final manuscript.
AI contribution statement: AI tools (specifically ChatGPT) were used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Xiamen University, No. 3502Z202373104.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: The datasets generated and analyzed during the current study are available from the corresponding authors upon reasonable request.
Corresponding author: Wei Wang, Professor, Department of Endocrinology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, No. 2000 Xiang’an East Road, Xiang’an District, Xiamen 361102, Fujian Province, China. wwang@xah.xmu.edu.cn
Received: April 7, 2026
Revised: May 14, 2026
Accepted: September 24, 2026
Published online: November 15, 2026
Processing time: 220 Days and 22.4 Hours
Revised: May 14, 2026
Accepted: September 24, 2026
Published online: November 15, 2026
Processing time: 220 Days and 22.4 Hours
Core Tip
Core Tip: This study examines the metabolic significance of elevated gonadotropin-releasing hormone (GnRH) in the postmenopausal state. We found that GnRH receptor is preferentially expressed in pancreatic β-cells and that GnRH enhances insulin secretion through the cAMP-PKA-PDX1 signaling pathway. These findings suggest that postmenopausal hypothalamic-pituitary-gonadal axis remodeling may contribute to β-cell compensation and provide a mechanistic link between reproductive endocrine aging and glucose homeostasis.