Zebrafish as a preclinical model for diabetes mellitus and its complications: From monogenic to gestational diabetes and beyond

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

Figure 1

Zebrafish as a model in diabetes research. A: Zebrafish as a model in diabetes due to genetic similarity with humans; B: Applications of zebrafish in modeling various types of diabetes; C: Diagram showing the resected zebrafish pancreas. T1DM: Type 1 diabetes mellitus; T2DM: Type 2 diabetes mellitus; GDM: Gestational diabetes mellitus; GCKD: Glomerular cystic kidney disease.

Figure 2

Drug modification approaches for inducing β-cell regeneration. DMFO: Difluoromethylornithine; STZ: Streptozotocin.

Figure 3

Small molecules promoting β-cell regeneration. Arx: Aristaless related homeobox; 12-LOX: 12-lipoxygenase.

Figure 4

Construction methods for zebrafish models of type 2 diabetes mellitus models. T2DM: Type 2 diabetes mellitus.