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Direct Sensing of Nutrients via a LAT1-like Transporter in Drosophila Insulin-Producing Cells

Abstract : 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.
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Gérard Manière, Anna b. Ziegler, Flore Geillon, David e. Featherstone, Yael Grosjean. Direct Sensing of Nutrients via a LAT1-like Transporter in Drosophila Insulin-Producing Cells. Cell Reports, Elsevier Inc, 2016, 17 (1), pp.137-148. ⟨10.1016/j.celrep.2016.08.093⟩. ⟨hal-01394085⟩

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