Fishing for Nature’s Hits: Establishment of the Zebrafish as a Model for Screening Antidiabetic Natural Products

Table 1

Comparison of different animal models for screening antidiabetic compounds.

Invertebrates	Zebrafish	Rodents	Large mammals (e.g., dogs and rabbits)
Silkworms can develop diabetes mellitus when fed a glucose-rich diet [17].	They can induce DM by simple immersion in high glucose water [18].	Developed diabetes mellitus within a few days by chemical injection or after a few weeks, via feeding a high-fat diet [19].	Developed diabetes mellitus by removing their pancreas [20].
Primary screening of antidiabetic drugs is possible [21].	High throughput screening for antidiabetic compounds is possible (e.g., [22]).	High throughput screening for antidiabetic compounds is not possible.	High throughput screening for antidiabetic compounds is not possible.
Requiring less time to develop diabetes mellitus compared to some mammalian models.	They require less time for screening and less amount of test compound relative to mammalian models.	Time consuming as it may take several days to develop diabetes mellitus via feeding [23].	They take several days to develop diabetes mellitus [23].
Inexpensive to use invertebrate models and less logistical requirements compared to mammals.	Inexpensive and easier to handle compared to mammalian models.	Expensive and harder to handle due to relatively large size (compared to fish or invertebrates).	Expensive and logistical/handling problems due to large size.
Reduced ethical issues compared to mammalian models.	Both adult and larval zebrafish are suitable for screening studies.	Some ethical issues depending on country of use (e.g., secured housing required in UK or USA) [24].	Ethical issues as an experimental model.
Amenable to fluorescence-based imaging and quantification of glucose uptake [25].	Fluorescence imaging of whole organism is possible for glucose uptake analysis; diabetes-related reporter gene based screening is also possible [26].	Mouse are amenable for fluorescence tracer-based imaging of whole-body insulin sensitivity and hepatic glucose production [27].	Fluorescent-based imaging of glucose homeostasis not possible.