Abstract
Animals adapt their growth rate and body size to available nutrients by a general modulation of insulin-insulin-like growth factor signaling. In Drosophila, dietary amino acids promote the release in the hemolymph of brain insulin-like peptides (Dilps), which in turn activate systemic organ growth. Dilp secretion by insulin-producing cells involves a relay through unknown cytokines produced by fat cells. Here, we identify Methuselah (Mth) as a secretin-incretin receptor subfamily member required in the insulin-producing cells for proper nutrient coupling. We further show, using genetic and ex vivo organ culture experiments, that the Mth ligand Stunted (Sun) is a circulating insulinotropic peptide produced by fat cells. Therefore, Sun and Mth define a new cross-organ circuitry that modulates physiological insulin levels in response to nutrients.
Copyright © 2016, American Association for the Advancement of Science.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipose Tissue / metabolism*
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Animals
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Brain / metabolism*
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / genetics
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Drosophila melanogaster / growth & development
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Drosophila melanogaster / metabolism*
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Eating
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Fasting / metabolism
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Fat Body / metabolism
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Food
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Hemolymph / metabolism
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Incretins / metabolism
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Inhibitor of Apoptosis Proteins / metabolism
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Insulin / metabolism*
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Ligands
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Organ Culture Techniques
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Positive Transcriptional Elongation Factor B / metabolism
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Pupa / genetics
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Pupa / growth & development
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Pupa / metabolism
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism*
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Receptors, Gastrointestinal Hormone / genetics
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Receptors, Gastrointestinal Hormone / metabolism*
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TOR Serine-Threonine Kinases / metabolism
Substances
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DIAP2 protein, Drosophila
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Drosophila Proteins
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Incretins
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Inhibitor of Apoptosis Proteins
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Insulin
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Ligands
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Membrane Proteins
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Receptors, G-Protein-Coupled
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Receptors, Gastrointestinal Hormone
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Tsp42Ej protein, Drosophila
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mth protein, Drosophila
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pgc protein, Drosophila
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secretin receptor
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target of rapamycin protein, Drosophila
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Positive Transcriptional Elongation Factor B
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TOR Serine-Threonine Kinases