The Zebrafish Model of Diabetes Mellitus: a Re-Appraisal

Review Article

Austin J Endocrinol Diabetes. 2020; 7(1): 1074.

The Zebrafish Model of Diabetes Mellitus: a Re-Appraisal

Sasmal S1 and Chakraverty R2*

¹Bengal College of Pharmaceutical Sciences and Research,India

²Department of Pharmacology, Institute of Post Graduate Medical Education & Research, India

*Corresponding author: Raja Chakraborty, ICMR Research Fellow, Department of Pharmacology, Institute of Post Graduate Medical Education & Research, Kolkata-700020. India

Received: April 28, 2020; Accepted: May 18, 2020; Published: May 25, 2020


The objective of this review is to explore multifactorial aspects concerning possible use of zebrafish as a model system for Diabetes Mellitus. For the purpose of this review, bibliographic searches were performed under Pubmed, Medline and Google scholar for articles indexed in these databases ranging from 2000 to 2019. Zebrafish has evolved as a suitable animal model organism for experimental pharmacology is expanding at a great rate to include lifestyle diseases of human. Lifestyle diseases are characterized by conditions which occur in primarily based on the way of living and occupational habits of individuals. Diseases that impact on our daily lifestyle are mainly obesity & diabetes. Nowadays, diabetes and obesity are considered as global epidemics. The prevalence rates of diabetes are increasing day by day in parallel with the rates of obesity. Research is ongoing for surgical and pathological management of obesity and diabetes. For identification and development of effective treatment the use of animal models are important. Zebrafish is poised to present as a unique model for human disease. In this study we discuss the advantages, disadvantages of pathology associated with diabetes & obesity by using zebrafish model. In consideration of these potential shortcomings, it is expected that zebrafish will not replace the classical mammalian test systems anytime soon, but rather complement them as a first step in vertebrate modelling of disease and aid the complex process of drug discovery.

Keywords: Danio rerio; Diabetes mellitus; Screening, Type 2 DM


The availability of a model predictive animal model of disease is regarded as a cornerstone in the drug discovery and development cycle. Zebrafish is a well-established and powerful model for the study of vertebrate biology. Scientifically zebrafish is known as Daniorerio which is belonging to the family Cyprinidae of the order Cypriniformes. Zebrafish is a vertebrate and having a high degree of physiological, anatomical and genetically based similarities to humans. It is reported that the organism shares 70% of the human genotype as also with 84% of genes are known to be associated with human disease [1].

Zebrafish has the capacity to produce hundreds of off springs in a week, they grow at extremely fast rate. Zebrafish has a short reproductive cycle and it is suitable for large scale drug screening. Zebrafish acquire unique characteristics that make this tropical fish a convenient animal model for developmental and genetic studies for the following reasons: this model organism reaches sexual maturity in about 2-3 months, the small size of this model allows for cultivating relatively large numbers in small area, female zebrafish are very fecund and can produce hundreds of eggs on weekly basis, egg fertilization process occurs externally which allows for the production of haploid embryos, the growing embryos are transparent, water soluble drugs are rapidly administered to zebrafish by adding them to water, zebrafish are susceptible to injection [2] and zebrafish are a fully sequenced genome.

Possible role in toxicology and drug discovery

Toxicological studies into zebrafish has only recently emerged for augmenting drug discovery. Drug effects on growth and development have been assessed by gross visual examination of the length and shape of the body segments of Danio rerio, the size and morphology of internal organs, including the brain, liver, cardiovascular system, cartilage, notochord, pancreas, intestine, and kidney. In addition, organ function assays have been and continue to be developed, which permit functional assessment of drug effects on the major internal organs in vivo. A large number of Phase I oxidation enzymes (e.g., the cytochrome P-450 family), Phase II conjugationhave been studied [3].

Zebrafish and a diabetes model [4]

Zebrafish is a proper model for studying metabolic dysfunction because they have appropriate organs that involve metabolism including increased adipose tissue, cardiovascular overload, steatosis, and energy homeostasis. The preservation of the structure of the pancreas and glucose homeostasis system make zebrafish convenient to identify novel targets in pancreas related diseases like type I & type II diabetes mellitus. Basic cellular architecture & morphogenesis of zebrafish pancreas is identical with mammalian pancreas which has both exocrine & endocrine compartments. Zebrafish pancreas function has been well-established by some methods which include fasting & postprandial glucose measurements and intra-peritoneal glucose tolerance tests and techniques for islet cell culture and pancreas dissection.

Type 1 diabetes mellitus model

Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease which is caused by destruction of insulin producing pancreatic β-cells. There are 3 methods of β-cells destruction: genetic ablation, chemical-dependent ablation and surgical removal. Chemicalinduced diabetes is widely used in zebrafish. In adult zebrafish intraperitoneal injection of Streptozotocin (STZ) is effective at β-cell ablation and causes reduction in insulin levels and there is elevation of fasting blood glucose levels. A total number of 6 administrations of Streptozotocin (STZ) within 4 weeks induces stable diabetic complications and hyperglycemia including nephropathy, retinopathy and impaired fin regeneration. It is the preferred method for modelling type 1 diabetes mellitus.

Type 2 diabetes mellitus model

Type 2 Diabetes Mellitus (T2DM) is characterized by resistance of insulin and β-cell dysfunction. Nutritional and genetic approaches have been used to generate Type 2 Diabetes Mellitus (T2DM) models in zebrafish. The most convenient method for modelling type 1 diabetes mellitus in zebrafish is immersion of zebrafish in glucose solution. Immersing of adult zebrafish into altering glucose concentrations of 0% and 2% every other day for 1 month or chronic exposure to glucose solution of 2% for 14 days induces elevated blood glucose levels, diabetic phenotypes and impaired response to exogenous insulin. Young zebrafish (4-11 months) accommodate to glucose exposure better than older zebrafish (1-3 years) (Table 1).

Citation: Sasmal S and Chakraverty R. The Zebrafish Model of Diabetes Mellitus: a Re-Appraisal. Austin J Endocrinol Diabetes. 2020; 7(1): 1074.