A glucose-sensing neuron pair regulates insulin and glucagon in Drosophila

Although glucose-sensing neurons were discovered more than 50 years ago, the physiological role of glucose sensing in metazoans remains unclear. Here, we identify a pair of glucose-sensing neurons (dubbed CN neurons) in the Drosophila brain with bifurcating axons whereby one axon branch projects to insulin-producing cells (IPCs) to trigger the release of Drosophila insulin-like peptide 2 (dilp2), and the other one extends to adipokinetic hormone (AKH)–producing cells to inhibit the secretion of AKH, fly’s analog of glucagon. These axonal branches undergo synaptic remodeling in response to changes in their internal energy status. Silencing of CN neurons largely disabled IPCs’ response to glucose and dilp2 secretion, and disinhibited AKH secretion in corpora cardiaca (CC), and caused hyperglycemia, a hallmark feature of diabetes mellitus. We propose that CN neurons maintain glucose homeostasis by promoting the secretion of dilp2 and suppressing the release of AKH when hemolymph glucose levels are high.