Abstract

A Drosophila model of diet-induced type 2 diabetes Kelly Laurenti1,2, Laura Palanker-Musselman2, Prasanna V. Ramachandran2, Jill L. Fink2, Zeke Maier3, Michael Brent3, and Thomas J. Baranski2 1Saint Louis University School of Medicine, 2Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine and 3Department of Computer Science and Engineering, Washington University School of Medicine We have developed a model of type 2 diabetes mellitus (T2DM) by feeding wild-type Drosophila a high sucrose diet. This resulted in larvae that were hyperglycemic, obese, and insulin resistant– hallmarks of T2DM. Expression levels of genes involved in lipogenesis were upregulated in high sucrose-fed larvae. To explore the relationship between diet and insulin resistance, we have knocked down the expression of a number of transcription factors that are likely to play a role in our model. These factors were selected based on a context likelihood of relatedness (CLR) algorithm, which is a network analysis of transcription factors that are affected by high sugar feeding. Our studies have focused on the fat body, which functions as both mammalian hepatocytes and adipocytes in the Drosophila larva. Transgenic RNAi was used to knockdown each of these genes individually in the fat body. Indeed, many did influence growth and fat storage on a high sucrose diet. These genes represent potential novel mediators of diet-induced diabetes in Drosophila.