Circulating Dilps, in conjunction with dietary amino acids, promote Dilp6
production by surface glial cells. This ligand activates InR on the surface of
cholinergic neurons, in close proximity to both the glia and the IPCs. IIS
within cholinergic neurons leads to Jeb secretion, which activates the Alk
receptor on IPCs. Downstream activation of the PI3K/AKT signaling pathway leads
to phosphorylation and nuclear exclusion of Foxo. In the absence of IIS, nuclear
Foxo negatively regulates the Ey and Dac transcription factors to suppress
dilp5 expression. IPC-derived Dilps are secreted into the
hemolymph via projections to the circulatory system (represented by the open
arrow), completing the positive feedback loop.