Journal Article

DZNE-2020-05117

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Direct Sensing of Nutrients via a LAT1-like Transporter in Drosophila Insulin-Producing Cells.

Manière, G. ; Ziegler, A. B.DZNE* ; Geillon, F. ; Featherstone, D. E. ; Grosjean, Y. (Corresponding author)

2016
Elsevier [New York, NY]

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Please use a persistent id in citations: doi:10.1016/j.celrep.2016.08.093

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.

Keyword(s): Amino Acid Transport Systems: genetics (MeSH) ; Amino Acid Transport Systems: metabolism (MeSH) ; Animals (MeSH) ; Brain: cytology (MeSH) ; Brain: metabolism (MeSH) ; Calcium: metabolism (MeSH) ; Drosophila Proteins: genetics (MeSH) ; Drosophila Proteins: metabolism (MeSH) ; Drosophila melanogaster: cytology (MeSH) ; Drosophila melanogaster: metabolism (MeSH) ; Gene Expression Regulation (MeSH) ; Glutamate Dehydrogenase: genetics (MeSH) ; Glutamate Dehydrogenase: metabolism (MeSH) ; Hemolymph: metabolism (MeSH) ; Insulin-Secreting Cells: cytology (MeSH) ; Insulin-Secreting Cells: metabolism (MeSH) ; Insulins: genetics (MeSH) ; Insulins: metabolism (MeSH) ; Larva: cytology (MeSH) ; Larva: metabolism (MeSH) ; Leucine: administration & dosage (MeSH) ; Leucine: metabolism (MeSH) ; Protein Isoforms: genetics (MeSH) ; Protein Isoforms: metabolism (MeSH) ; Signal Transduction (MeSH) ; Amino Acid Transport Systems ; Drosophila Proteins ; Ilp5 protein, Drosophila ; Insulins ; Mnd protein, Drosophila ; Protein Isoforms ; Glutamate Dehydrogenase ; Leucine ; Calcium

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Contributing Institute(s):

1. Dynamics of neuronal circuits (AG Tavosanis)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2016

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Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; DOAJ Seal ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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