Dietary sugar promotes systemic TOR activation in Drosophila through AKH-dependent selective secretion of Dilp3

Nat Commun. 2015 Apr 17;6:6846. doi: 10.1038/ncomms7846.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autophagy
  • Corpora Allata / cytology
  • Corpora Allata / metabolism
  • Dietary Sucrose / metabolism*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Insect Hormones / metabolism*
  • Insulin-Secreting Cells / metabolism*
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Larva
  • Oligopeptides / metabolism*
  • Pyrrolidonecarboxylic Acid / analogs & derivatives*
  • Pyrrolidonecarboxylic Acid / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*


  • Dietary Sucrose
  • Drosophila Proteins
  • ILP3 protein, Drosophila
  • Insect Hormones
  • Intercellular Signaling Peptides and Proteins
  • Oligopeptides
  • DAKH peptide
  • target of rapamycin protein, Drosophila
  • TOR Serine-Threonine Kinases
  • Pyrrolidonecarboxylic Acid