title: Dietary sugar promotes systemic TOR activation in Drosophila through AKH-dependent selective secretion of Dilp3.
abstract: Secreted ligands of the insulin family promote cell growth and maintain sugar homeostasis. Insulin release is tightly regulated in response to dietary conditions, but how insulin-producing cells (IPCs) coordinate their responses to distinct nutrient signals is unclear. Here we show that regulation of insulin secretion in Drosophila larvae has been segregated into distinct branches-whereas amino acids promote the secretion of Drosophila insulin-like peptide 2 (Dilp2), circulating sugars promote the selective release of Dilp3. Dilp3 is uniquely required for the sugar-mediated activation of TOR signalling and suppression of autophagy in the larval fat body. Sugar levels are not sensed directly by the IPCs, but rather by the adipokinetic hormone (AKH)-producing cells of the corpora cardiaca, and we demonstrate that AKH signalling is required in the IPCs for sugar-dependent Dilp3 release. Thus, IPCs integrate multiple cues to regulate the secretion of distinct insulin subtypes under varying nutrient conditions.
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, 6-160 Jackson Hall, 321 Church St SE, Minneapolis, Minnesota 55455, USA.
authors.forename: Jung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, 6-160 Jackson Hall, 321 Church St SE, Minneapolis, Minnesota 55455, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Neufeld
mesh_terms: D000818:Animals; D001343:Autophagy; D003335:Corpora Allata / Q000166:cytology / Q000378:metabolism; D019422:Dietary Sucrose / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D007301:Insect Hormones / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007814:Larva; D009842:Oligopeptides / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D019422:Dietary Sucrose; D029721:Drosophila Proteins; C542424:ILP3 protein, Drosophila; D007301:Insect Hormones; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; C065368:DAKH peptide; C416303:target of rapamycin protein, Drosophila; D058570:TOR Serine-Threonine Kinases; D011761:Pyrrolidonecarboxylic Acid