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Summary Dietary leucine has been suspected to play an important role in insulin release, a hormone that controls satiety and metabolism. The mechanism by which insulin-producing cells (IPCs) sense leucine and regulate insulin secretion is still poorly understood. In Drosophila, insulin-like peptides (DILP2 and DILP5) are produced by brain IPCs and are released in the hemolymph after leucine ingestion. Using Ca2+-imaging and ex vivo cultured larval brains, we demonstrate that IPCs can directly sense extracellular leucine levels via minidiscs (MND), a leucine transporter. MND knockdown in IPCs abolished leucine-dependent changes, including loss of DILP2 and DILP5 in IPC bodies, consistent with the idea that MND is necessary for leucine-dependent DILP release. This, in turn, leads to a strong increase in hemolymph sugar levels and reduced growth. GDH knockdown in IPCs also reduced leucine-dependent DILP release, suggesting that nutrient sensing is coupled to the glutamate dehydrogenase pathway., Graphical Abstract, Highlights • IPCs directly sense extracellular leucine levels via minidiscs (MND) • MND knockdown in IPCs abolishes loss of DILP2 and DILP5 • This leads to a strong increase in hemolymph sugar levels and reduces growth • GDH knockdown in IPCs reduces leucine-dependent DILP release, Manière et al. find that leucine induces the disappearance of two DILPs in Drosophila IPCs. Minidiscs (MND) is the primary leucine sensor, and downregulation has consequences for glycemia and growth. The authors propose that the leucine/MND pathway represents a conserved mechanism for insulin release.