Wild-Type Zebrafish (Danio rerio) Larvae as a Vertebrate Model for Diabetes and Comorbidities: A Review

SIMPLE SUMMARY: Diabetes is predicted to become a major global pandemic in the not too distant future; subsequently, there is an urgent need to develop new drugs to treat this disease and its associated complications. Animal studies form an integral component of drug development, as they provide information concerning safety and efficacy of new drugs in an experimental setting reflecting the complexity of human physiology. Over the past decade, research has firmly established that zebrafish represent a convenient preclinical animal model. While genetic manipulation has given rise to numerous target specific models, these mutant zebrafish are unfortunately also associated with serious disadvantages. Therefore, wild-type zebrafish may be a preferred option for many researchers; however, information relating to their use in diabetes research remains scattered. This review collates existing scientific literature specifically pertaining to wild-type zebrafish and highlights the value of wild-type zebrafish larvae as a suitable animal model. Details regarding organ development, including similarities to mammalian counterparts, are discussed to indicate relevance. In addition, information covering experimental design and endpoint analysis provides an overview of the technical aspects when using wild-type zebrafish larvae as an experimental tool to mimic diabetes and its associated complications. ABSTRACT: Zebrafish have become a popular alternative to higher animals in biomedical and pharmaceutical research. The development of stable mutant lines to model target specific aspects of many diseases, including diabetes, is well reported. However, these mutant lines are much more costly and challenging to maintain than wild-type zebrafish and are simply not an option for many research facilities. As an alternative to address the disadvantages of advanced mutant lines, wild-type larvae may represent a suitable option. In this review, we evaluate organ development in zebrafish larvae and discuss established methods that use wild-type zebrafish larvae up to seven days post fertilization to test for potential drug candidates for diabetes and its commonly associated conditions of oxidative stress and inflammation. This provides an up to date overview of the relevance of wild-type zebrafish larvae as a vertebrate antidiabetic model and confidence as an alternative tool for preclinical studies. We highlight the advantages and disadvantages of established methods and suggest recommendations for future developments to promote the use of zebrafish, specifically larvae, rather than higher animals in the early phase of antidiabetic drug discovery.