Kyu-Sun Lee
1,6, O-Yu Kwon
2,6, Joon H. Lee
3,6, Kisang Kwon
2, Kyung-Jin Min
4,7, Sun-Ah Jung
3, Ae-Kyeong Kim
1, Kwan-Hee You
5, Marc Tatar
4 & Kweon Yu
1
Insulin and insulin growth factor have central roles in growth
1, 2, metabolism
3 and ageing
4, 5 of animals, including
Drosophila melanogaster. In
Drosophila, insulin-like peptides (Dilps) are produced by specialized neurons in the brain
3, 6. Here we show that
Drosophila short neuropeptide F (sNPF), an orthologue of mammalian neuropeptide Y (NPY), and sNPF receptor sNPFR1 regulate expression of
Dilps. Body size was increased by overexpression of
sNPF or
sNPFR1. The fat body of
sNPF mutant
Drosophila had downregulated Akt, nuclear localized FOXO, upregulated translational inhibitor
4E-BP and reduced cell size. Circulating levels of glucose were elevated and lifespan was also extended in
sNPF mutants. We show that these effects are mediated through activation of extracellular signal-related kinases (ERK) in insulin-producing cells of larvae and adults. Insulin expression was also increased in an ERK-dependent manner in cultured
Drosophila central nervous system (CNS) cells and in rat pancreatic cells treated with sNPF or NPY peptide, respectively.
Drosophila sNPF and the evolutionarily conserved mammalian NPY seem to regulate ERK-mediated insulin expression and thus to systemically modulate growth, metabolism and lifespan.
1. Centre for Regenerative Medicine, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-333, Korea.
2. Department of Anatomy, College of Medicine, Chungnam National University, Daejeon, Korea.
3. Myung-Gok Eye Research Institute, Kim''s Eye Hospital, College of Medicine, Konyang University, Chungnam, Korea.
4. Department of Ecology and Evolutionary Biology, Brown University, Providence, RI 02912, USA.
5. School of Bioscience and Biotechnology, Chungnam National University, Daejeon, Korea.
6. These authors contributed equally to this work.
7. Present address: Department of Biological Sciences, University of Alaska at Anchorage, Anchorage, AK 99508, USA.
Correspondence to: Kweon Yu1
