Zebrafish as an effective model for accelerating diabetes research from discovery to therapy.

Background: Diabetes is a global health crisis affecting over 422 million people, necessitating innovative research models. Zebrafish (Danio rerio) have emerged as a powerful tool due to their genetic tractability, physiological similarity to humans, and suitability for high-throughput studies. Methods: A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science, focusing on studies involving zebrafish models of Type 1 and Type 2 diabetes. Included publications were evaluated based on their methodology (e.g., surgical, chemical, genetic, or dietary induction of diabetes), reproducibility, and relevance to diabetic pathophysiology and complications. Results: Zebrafish models effectively replicate core diabetic features, including hyperglycemia, insulin resistance, and β-cell dysfunction. Their transparent embryos and larvae facilitate real-time visualization of metabolic and vascular changes. Furthermore, zebrafish support the study of diabetes-related complications-such as retinopathy, nephropathy, neuropathy, and cardiomyopathy-through genetic modifications and pharmacological interventions. Studies have demonstrated the efficacy of antidiabetic drugs, including metformin and glimepiride, using these models. Conclusion: Despite challenges (e.g., physiological differences from mammals), zebrafish bridge mechanistic discovery and translational applications, accelerating diabetes research. Their cost-effectiveness, rapid development, and screening potential underscore their critical role in understanding diabetes and developing targeted therapies to address this global health burden.