View Program - 63rd Annual Drosophila Research Conference

The insulin/IGF1 signaling pathway regulates cell and organismal growth in animals ranging from fruit flies to humans. Insulin-like hormones are secreted in response to dietary nutrients and drive anabolic metabolism. In Drosophila, seven insulin-like peptides (Dilps) activate the insulin/IGF signaling pathway through a single known insulin receptor. We previously reported that Toll signaling in Drosophila larval fat body inhibited whole-animal growth by reducing circulating levels of fat body-derived Dilp6. In contrast, Dilp2 secretion from insulin producing cells was not affected by Toll pathway activation in larval fat body. To determine whether other physiological conditions differently regulated these two related hormones, we asked how Dilp2 and Dilp6 respond to starvation and specific dietary nutrients. We used dual-epitope tagged Dilp2 and Dilp6 alleles to measure hemolymph levels of each hormone in male and female larvae. Starvation of mid-third instar larvae on agar led to a 50% reduction in circulating Dilp2 after 6 hours and a 90% reduction in Dilp2 after 24 hours. In contrast, circulating Dilp6 levels were unchanged over the course of 24 hours of starvation on agar. Next, we asked whether Dilp2 and Dilp6 respond to specific dietary nutrients. We fed larvae sucrose, peptone or yeast extract in agar and compared hormone levels with fed and starved conditions. Hemolymph Dilp2 was partially recovered by feeding larvae peptone or yeast extract but not sucrose. Circulating levels of Dilp6 were modestly increased by a sucrose-only diet, but surprisingly, peptone or yeast extract feeding repressed Dilp6. The reduced circulating level of Dilp6 caused by the high protein, yeast extract diet was partially rescued when sucrose was added back. These data suggest that Dilp2 and Dilp6 secretion are regulated differently by environmental conditions ranging from infection to dietary composition. Two open questions are how Dilp2 and Dilp6 secretion are regulated by specific nutrients and how the single known insulin receptor integrates divergent signals from distinct Dilps to control growth and metabolism.

Distinct dietary nutrients regulate circulating levels of Dilp2 and Dilp6 in Drosophila larvae

**Distinct dietary nutrients regulate circulating levels of Dilp2 and Dilp6 in Drosophila larvae**