title: Drosophila insulin release is triggered by adipose Stunted ligand to brain Methuselah receptor.
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.
authors.affiliation: Université Côte d'Azur, CNRS, INSERM, Institute of Biology Valrose (iBV), 06100 Nice, France. delanoue@unice.fr leopold@unice.fr.
authors.forename: Renald
authors.initials: R
authors.lastname: Delanoue
authors.affiliation: Université Côte d'Azur, CNRS, INSERM, Institute of Biology Valrose (iBV), 06100 Nice, France.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Meschi
authors.affiliation: Université Côte d'Azur, CNRS, INSERM, Institute of Biology Valrose (iBV), 06100 Nice, France.
authors.forename: Neha
authors.initials: N
authors.lastname: Agrawal
authors.affiliation: Université Côte d'Azur, CNRS, INSERM, Institute of Biology Valrose (iBV), 06100 Nice, France.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mauri
authors.affiliation: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
authors.forename: Yonit
authors.initials: Y
authors.lastname: Tsatskis
authors.affiliation: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: McNeill
authors.affiliation: Université Côte d'Azur, CNRS, INSERM, Institute of Biology Valrose (iBV), 06100 Nice, France. delanoue@unice.fr leopold@unice.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Léopold
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004435:Eating; D005215:Fasting / Q000378:metabolism; D005216:Fat Body / Q000378:metabolism; D005502:Food; D006458:Hemolymph / Q000378:metabolism; D054795:Incretins / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009924:Organ Culture Techniques; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D011679:Pupa / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C111892:DIAP2 protein, Drosophila; D029721:Drosophila Proteins; D054795:Incretins; D051034:Inhibitor of Apoptosis Proteins; D007328:Insulin; D008024:Ligands; D008565:Membrane Proteins; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C502091:Tsp42Ej protein, Drosophila; C115381:mth protein, Drosophila; C527201:pgc protein, Drosophila; C029937:secretin receptor; C416303:target of rapamycin protein, Drosophila; D042925:Positive Transcriptional Elongation Factor B; D058570:TOR Serine-Threonine Kinases