The mechanisms that suppress insulin secretion during starvation are incompletely understood, but it has been postulated that enteroendocrine ‘decretin’ hormones may be involved. Here, Alfa et al. identify the decretin hormone limostatin (Lst) in Drosophila melanogaster. They show that Lst is secreted by gut-associated endocrine cells following nutrient restriction, and suppresses insulin release from insulin-producing cells through interaction with a conserved G protein-coupled receptor encoded by CG9918. The most similar mammalian orthologue to CG9918 is the neuromedin U (NMU) receptor, which is expressed in islet beta cells. NMU suppressed insulin secretion in purified human islets and is a candidate mammalian decretin.