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Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. May 15, 2025; 16(5): 100574
Published online May 15, 2025. doi: 10.4239/wjd.v16.i5.100574
Zebrafish as a preclinical model for diabetes mellitus and its complications: From monogenic to gestational diabetes and beyond
Jie Huang, Yin-Ling Chen
Jie Huang, Yin-Ling Chen, School of Medicine, Hangzhou City University, Hangzhou 310000, Zhejiang Province, China
Author contributions: Huang J analyzed the literature and wrote the manuscript; Chen YL designed the study; both authors contributed significantly to the literature analysis and reviewed and approved the final manuscript.
Supported by Natural Science Foundation of Zhejiang Province, China, No. LQ24H070007.
Conflict-of-interest statement: Both 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: Yin-Ling Chen, PhD, Lecturer, School of Medicine, Hangzhou City University, No. 51 Huzhou Road, Hangzhou 310000, Zhejiang Province, China. chenyinling6666@163.com
Received: August 21, 2024
Revised: December 13, 2024
Accepted: March 19, 2025
Published online: May 15, 2025
Processing time: 247 Days and 21.4 Hours
Abstract

With diabetes currently affecting 537 million people globally, innovative research approaches are urgently required. Zebrafish (Danio rerio) has emerged as a pivotal model organism in diabetes research, particularly valuable for developmental biology studies and preclinical therapeutic validation. Its rapid life cycle, optical transparency, and genetic tractability collectively enable efficient longitudinal observation of pathological progression and pharmacological responses. Utilizing zebrafish models, researchers have elucidated fundamental mechanisms governing islet development, β-cell dysfunction, and metabolic dysregulation. These experimental systems have significantly advanced our understanding of various diabetes subtypes, including type 1, type 2, gestational, and monogenic forms, while also facilitating mechanistic studies of diabetic complications such as retinopathy and nephropathy. Recent model refinements, particularly in simulating monogenic disorders and pregnancy-associated metabolic changes, promise to deepen our comprehension of disease pathophysiology and therapeutic interventions. Nevertheless, a persistent limitation lies in their incomplete recapitulation of human-specific physiological complexity and multi-organ metabolic interactions, factors that may influence translational applicability. Despite these constraints, zebrafish-based research continues to provide an indispensable platform for diabetes investigation, holding significant promise for alleviating the escalating global burden of this metabolic disorder.

Keywords: Zebrafish; Preclinical model; Diabetes mellitus; Monogenic diabetes; Gestational diabetes

Core Tip: Notably, zebrafish has been established as a model organism in diabetes research, providing unique insights into pathological progression, therapeutic efficacy evaluation, and complication pathogenesis owing to its accelerated developmental cycles, optical clarity, and genetic tractability. Particularly, its experimental versatility has enabled successful recapitulation of type 1 and type 2 diabetes pathogenesis while providing platforms for systematic investigation of monogenic variants and pregnancy-associated metabolic dysregulation. Collectively, these scientific advancements represent transformative potential for advancing mechanistic comprehension and developing targeted interventions against diabetes mellitus and its secondary complications.