Antagonistic insulin-like signaling influencing glucose regulation in C. elegans

The insulin/ IGF-signaling (IIS) is an evolutionary conserved signaling pathway within eukaryotic organisms that regulates glucose metabolism and cell division. The nematode, C. elegans is an excellent model for exploring IIS as they have 40 insulin-like peptides that act on a single receptor, DAF-2. We aim to explore the relationships between IIS and glucose metabolism, focusing on the antagonistic insulin-like peptide, INS-17 and its influence over FDGT-1 (facilitated glucose transporter 1). FDGT-1 is expressed throughout the nematode, including the basolateral membrane of intestinal cells and where it is theorized to export glucose to the surrounding somatic cells rather than absorb it from the intestinal tract. We hypothesize that IIS controls transcription of FDGT-1 and antagonistic peptides should lead to a decrease in FDGT-1 transcription, resulting in the increased lifespan and increased fat accumulation observed in daf-2(lf) loss of function and ins-17(oe) over expressing strains. In this study, survival assays are used to assess the impact which high-glucose content has on lifespan, along with Oil Red O (ORO) lipid staining to visualize lipid accumulation amongst conditions and protein quantification of FDGT-1:GFP to evaluate FDGT-1 protein levels. Our findings are consistent with the idea of low insulin signaling leading to extended lifespan as daf-2(lf) lived significantly longer than WT in both 0% and 2% glucose conditions and ins-17(oe) living significantly longer than wildtype in 2% glucose conditions. The ORO lipid staining revealed that high glucose conditions and low insulin signaling result in lipid accumulation within the nematode. Using the fdgt-1:gfp strain, we were able to determine an increase in the FDGT-1 in the presence of glucose, suggesting FDGT-1 expression is influenced by glucose. These findings aim to further our understanding of IIS regulating glucose uptake and metabolism, along with the significance of the FDGT-1 glucose transporter.