A Comprehensive Review of Preclinical Animal Models Used in Diabetic Research

The hallmark of diabetes mellitus, a chronic condition, is either a deficiency in insulin secretion or action, or both. The preclinical screening of anti-diabetic agents requires suitable models. Currently used models employ rodents (mice and rats), higher animals such as pigs and dogs, zebrafish, and invertebrates such as Drosophila and C. elegans . Diabetes mellitus is marked by a multifaceted pathogenesis. One model alone is not sufficient to screen a treatment method or identify the mechanism of disease progression. Therefore, multiple models employ methods such as induction using diabetogenic chemicals, surgical methods, viruses, spontaneous autoimmune animals, genetic manipulation, and induction by a combination of streptozotocin (STZ) and a high-fat diet (HFD) or low-protein diet. STZ has the potential to produce a stable model of both type 1 and type 2 diabetes mellitus. Alloxan (ALX), a cytotoxic glucose analogue like STZ, destroys pancreatic β-cells. A disadvantage of this approach is that chemical diabetogenic agents destroy cells other than β-cells. Transgenic animals are more expensive to develop. Spontaneous autoimmune rodents are also used as diabetic models. New targets for the management of diabetes mellitus can be found using the diabetes model in zebrafish. The use of invertebrates has advantages such as economy, short generation time, and high fertility, but their anatomy and physiology are different from those of humans. The article is prepared by reviewing publications in PUBMED and Google Scholar from 2000 to 2025.