Genetic ablation of Drosophila melanogaster insulin-like peptide (DILP) and adipokinetic hormone-producing cells accompanied by cell biological and metabolic measurements have revealed functional conservation in nutrient sensing and the underlying signaling mechanisms between mammal and fruit fly. Despite significant advances gained in understanding the neuroendocrine responses to nutrient changes during developmental larval stages, we discuss here the need for investigating glucose homeostasis in the post-mitotic adult stage as the result of ablation of DILP producing cells (IPCs). Our recent studies demonstrate that while both constitutive and adult-specific partial ablation of IPCs renders those flies hyperglycemic and glucose intolerant, flies with adult-specific IPC ablation remain insulin sensitive. Our results substantiate a role of adult IPCs in modulating aspects of glucose homeostasis and highlight the complexity in DILP action in the adult fly.