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@ARTICLE{Manire:138795,
      author       = {Manière, Gérard and Ziegler, Anna B and Geillon, Flore
                      and Featherstone, David E and Grosjean, Yael},
      title        = {{D}irect {S}ensing of {N}utrients via a {LAT}1-like
                      {T}ransporter in {D}rosophila {I}nsulin-{P}roducing
                      {C}ells.},
      journal      = {Cell reports},
      volume       = {17},
      number       = {1},
      issn         = {2211-1247},
      address      = {[New York, NY]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2020-05117},
      pages        = {137-148},
      year         = {2016},
      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
                      Ca(2+)-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.},
      keywords     = {Amino Acid Transport Systems: genetics / Amino Acid
                      Transport Systems: metabolism / Animals / Brain: cytology /
                      Brain: metabolism / Calcium: metabolism / Drosophila
                      Proteins: genetics / Drosophila Proteins: metabolism /
                      Drosophila melanogaster: cytology / Drosophila melanogaster:
                      metabolism / Gene Expression Regulation / Glutamate
                      Dehydrogenase: genetics / Glutamate Dehydrogenase:
                      metabolism / Hemolymph: metabolism / Insulin-Secreting
                      Cells: cytology / Insulin-Secreting Cells: metabolism /
                      Insulins: genetics / Insulins: metabolism / Larva: cytology
                      / Larva: metabolism / Leucine: administration $\&$ dosage /
                      Leucine: metabolism / Protein Isoforms: genetics / Protein
                      Isoforms: metabolism / Signal Transduction / Amino Acid
                      Transport Systems (NLM Chemicals) / Drosophila Proteins (NLM
                      Chemicals) / Ilp5 protein, Drosophila (NLM Chemicals) /
                      Insulins (NLM Chemicals) / Mnd protein, Drosophila (NLM
                      Chemicals) / Protein Isoforms (NLM Chemicals) / Glutamate
                      Dehydrogenase (NLM Chemicals) / Leucine (NLM Chemicals) /
                      Calcium (NLM Chemicals)},
      cin          = {AG Tavosanis},
      ddc          = {610},
      cid          = {I:(DE-2719)1013018},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:27681427},
      pmc          = {pmc:PMC5055474},
      doi          = {10.1016/j.celrep.2016.08.093},
      url          = {https://pub.dzne.de/record/138795},
}