Diabetes Screening Method
As type 2 diabetes is a systemic disease, traditional cell culture models do not adequately recap the disease to find good drug candidates. Moreover, mouse, rat and monkey in vivo models are too expensive for high-throughput screening. Researchers at Leiden University found a new zebraphic model for insulin resistance, a hallmark or type 2 diabetes. Using injection technology, this model is currently being used to discover new targets and new generic small-molecule compounds. Secondly, this model is very suitable for compound screening in whole zebrafish organisms.
The researchers from Leiden University have tested 1000+ FDA approved compounds, suitable for drug repurposing, with a hit rate of about 1%. Insulin resistant zebrafish diabetic larvae are produced using our proprietary method. They are robotically injected with a compound and, some hours later, with fluorescent glucose in the yolk area. After 30 minutes, the fluorescent glucose is imaged using automated microscopy. Although in control larvae, the glucose is taken up in the cells, in the insulin resistant larvae, the glucose is not. For some 'hit' compounds, added to mutant larvae, the uptake in the cells is rescued; insulin resistance is reversed.
Given the highly conserved nature of the signal transduction pathways targeted with these compounds the results are highly likely to be translatable to effects in human patients.
The researchers also aim to screen for new small molecule entities and new targets. Due to recent advances in zebrafish genetics, screen high throughput for target is also possible.
Identify therapeutics that affect the cause of type 2 diabetes, by reducing or reversing insulin resistance.
Extend the use of this method to other systemic metabolic diseases, eg wasting syndrome, auto-inflammatory diseases and wound repair.
- The simplicity of the experiment combined with automation technology allows to screen up to 1000 compounds per month, with one single setup.
- We capitalize on the fast cycle of zebrafish and proprietary automation technology for fast therapeutics selection or anti-diabetic drugs.
- Potential use to perform screening in other systemic metabolic diseases.