TY  - JOUR
AU  - Manière, Gérard
AU  - Ziegler, Anna B
AU  - Geillon, Flore
AU  - Featherstone, David E
AU  - Grosjean, Yael
TI  - Direct Sensing of Nutrients via a LAT1-like Transporter in Drosophila Insulin-Producing Cells.
JO  - Cell reports
VL  - 17
IS  - 1
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DZNE-2020-05117
SP  - 137-148
PY  - 2016
AB  - 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.
KW  - Amino Acid Transport Systems: genetics
KW  - Amino Acid Transport Systems: metabolism
KW  - Animals
KW  - Brain: cytology
KW  - Brain: metabolism
KW  - Calcium: metabolism
KW  - Drosophila Proteins: genetics
KW  - Drosophila Proteins: metabolism
KW  - Drosophila melanogaster: cytology
KW  - Drosophila melanogaster: metabolism
KW  - Gene Expression Regulation
KW  - Glutamate Dehydrogenase: genetics
KW  - Glutamate Dehydrogenase: metabolism
KW  - Hemolymph: metabolism
KW  - Insulin-Secreting Cells: cytology
KW  - Insulin-Secreting Cells: metabolism
KW  - Insulins: genetics
KW  - Insulins: metabolism
KW  - Larva: cytology
KW  - Larva: metabolism
KW  - Leucine: administration & dosage
KW  - Leucine: metabolism
KW  - Protein Isoforms: genetics
KW  - Protein Isoforms: metabolism
KW  - Signal Transduction
KW  - Amino Acid Transport Systems (NLM Chemicals)
KW  - Drosophila Proteins (NLM Chemicals)
KW  - Ilp5 protein, Drosophila (NLM Chemicals)
KW  - Insulins (NLM Chemicals)
KW  - Mnd protein, Drosophila (NLM Chemicals)
KW  - Protein Isoforms (NLM Chemicals)
KW  - Glutamate Dehydrogenase (NLM Chemicals)
KW  - Leucine (NLM Chemicals)
KW  - Calcium (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:27681427
C2  - pmc:PMC5055474
DO  - DOI:10.1016/j.celrep.2016.08.093
UR  - https://pub.dzne.de/record/138795
ER  -