Use ofDrosophilaas an Evaluation Method Revealsimpas a Candidate Gene for Type 2 Diabetes in Rat LocusNiddm22

Abstract

Type 2 diabetes (T2D) is one of the most common human diseases. QTL analysis of the diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats has identified numerous hyperglycemic loci. However, molecular characterization and/or gene identification largely remains to be elucidated due mostly to the weak genetic variances contributed by each locus. Here we utilizedDrosophila melanogasteras a secondary model organism for functional evaluation of the candidate gene. We demonstrate that the tissue specific knockdown of a homologue ofigf2bp2RNA binding protein leads to increased sugar levels similar to that found in the OLETF rat. In the mutant, the expression of two of the insulin-like peptides encoded in the fly genome,dilp2anddilp3, were found to be downregulated. Consistent with previous reports ofdilpmutants, theimpmutant flies exhibited an extension of life span; in contrast, starvation tolerance was reduced. These results further reinforce the possibility thatimpis involved in sugar metabolism by modulating insulin expression.