Direct Sensing of Nutrients via a LAT1-like Transporter in Drosophila Insulin-Producing Cells.
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.
CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France; INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France; Université de Bourgogne Franche-Comté, UMR Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France.
Gérard
G
Manière
CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France; INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France; Université de Bourgogne Franche-Comté, UMR Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France.
Anna B
AB
Ziegler
CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France; INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France; Université de Bourgogne Franche-Comté, UMR Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France.
Flore
F
Geillon
Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
David E
DE
Featherstone
CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France; INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France; Université de Bourgogne Franche-Comté, UMR Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France. Electronic address: yael.grosjean@u-bourgogne.fr.
Yael
Y
Grosjean
D026905:Amino Acid Transport Systems / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D005969:Glutamate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D006458:Hemolymph / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D061385:Insulins / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000166:cytology / Q000378:metabolism; D007930:Leucine / Q000008:administration & dosage / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D026905:Amino Acid Transport Systems; D029721:Drosophila Proteins; C570846:Ilp5 protein, Drosophila; D061385:Insulins; C542117:Mnd protein, Drosophila; D020033:Protein Isoforms; D005969:Glutamate Dehydrogenase; D007930:Leucine; D002118:Calcium
Drosophila; Drosophila insulin-like peptides; amino acid transporter; food; glutamate dehydrogenase; glycemia; growth; insulin-producing cells; minidiscs; starvation
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