Opposing effects of dietary protein and sugar regulate a transcriptional target of Drosophila insulin-like peptide signaling

Cell Metab. 2008 Apr;7(4):321-32. doi: 10.1016/j.cmet.2008.02.012.


Specific neurosecretory cells of the Drosophila brain express insulin-like peptides (dilps), which regulate growth, glucose homeostasis, and aging. Through microarray analysis of flies in which the insulin-producing cells (IPCs) were ablated, we identified a target gene, target of brain insulin (tobi), that encodes an evolutionarily conserved alpha-glucosidase. Flies with lowered tobi levels are viable, whereas tobi overexpression causes severe growth defects and a decrease in body glycogen. Interestingly, tobi expression is increased by dietary protein and decreased by dietary sugar. This pattern is reminiscent of mammalian glucagon secretion, which is increased by protein intake and decreased by sugar intake, suggesting that tobi is regulated by a glucagon analog. tobi expression is also eliminated upon ablation of neuroendocrine cells that produce adipokinetic hormone (AKH), an analog of glucagon. tobi is thus a target of the insulin- and glucagon-like signaling system that responds oppositely to dietary protein and sugar.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dietary Carbohydrates / metabolism
  • Dietary Carbohydrates / pharmacology*
  • Dietary Proteins / metabolism
  • Dietary Proteins / pharmacology*
  • Drosophila / enzymology
  • Drosophila / genetics*
  • Drosophila Proteins / metabolism
  • Enzyme Activation
  • Fat Body / metabolism
  • Female
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Insect Hormones / metabolism
  • Larva / metabolism
  • Longevity
  • Male
  • Neurosecretory Systems / drug effects
  • Neurosecretory Systems / metabolism
  • Oligopeptides / metabolism
  • Pyrrolidonecarboxylic Acid / analogs & derivatives
  • Pyrrolidonecarboxylic Acid / metabolism
  • RNA Interference
  • Signal Transduction* / drug effects
  • Somatomedins / genetics
  • Somatomedins / metabolism*
  • alpha-Glucosidases / genetics*
  • alpha-Glucosidases / metabolism


  • Dietary Carbohydrates
  • Dietary Proteins
  • Drosophila Proteins
  • FOXO protein, Drosophila
  • Forkhead Transcription Factors
  • Insect Hormones
  • Oligopeptides
  • Somatomedins
  • adipokinetic hormone
  • alpha-Glucosidases
  • Pyrrolidonecarboxylic Acid

Associated data

  • GEO/GSE10625