MEDROS has developed and characterized a useful model of diet-induced obesity and insulin resistance (type 2 diabetes) in Drosophila. Feeding a high sugar diet to Drosophila results in many metabolic changes that mimic those seen in mammalian model systems and humans including hyperglycemia, hyperinsulinemia, increased triglycerides and free fatty acids, increased lipid droplets in the liver ortholog, aspects of kidney/liver/heart disease, and shortened lifespan. In addition, a developmental delay occurs in Drosophila in response to high sugar feeding; in a screen, compounds that rescue the developmental delay are scored as hits.

Using a classical genetic approach, the MEDROS founders individually tested mutations in 7,128 genes for their effects on the sugar-mediated developmental delay. 318 genetic modifiers (suppressors and enhancers) have been identified. Therefore, this model allows simultaneous screening of a large number of targets relevant to diet-induced insulin resistance. An initial screen of a 6,500 compound commercial library has been conducted using the diabetes model. Hits were obtained and these are under evaluation in secondary assays.

Fly kidney: ‘nephrocyte’ (podocyte) probed for Nephrin, Neph1, and the nuclear DAPI stain.

Individual nephrocytes expressing Neph1.

Individual nephrocytes expressing Nephrin.

images courtesy of Jianbo Na