InR

Summary

Gene Symbol: InR
Description: Insulin-like receptor
Alias: 18402, CG18402, DIHR, DILR, DIR, DIRH, DIRbeta, DInR, DInr, Dir-a, Dir-b, Dmel\CG18402, INR, INS, Inr, Inr-alpha, Inr-beta, InsR, dINR, dIR, dIRH, dInR, dInr, dInsR, dinr, dir, er10, inR, inr, insulin/insulin-like growth factor receptor, l(3)05545, l(3)93Dj, l(3)er10, lnR, sprout, Insulin-like receptor, CG18402-PA, CG18402-PB, CG18402-PC, CG18402-PD, InR-PA, InR-PB, InR-PC, InR-PD, Insulin-receptor, drosophila insulin receptor, insulin, insulin receptor, insulin receptor homolog, insulin receptor homologue, insulin-like receptor, lethal(3)93Dj, sprout
Species: fruit fly

Top Publications

  1. Root C, Ko K, Jafari A, Wang J. Presynaptic facilitation by neuropeptide signaling mediates odor-driven food search. Cell. 2011;145:133-44 pubmed publisher
    ..We found that a local signal by short neuropeptide F (sNPF) and a global metabolic cue by insulin are integrated at specific odorant receptor neurons (ORNs) to modulate olfactory sensitivity...
  2. Boulan L, Martin D, Milan M. bantam miRNA promotes systemic growth by connecting insulin signaling and ecdysone production. Curr Biol. 2013;23:473-8 pubmed publisher
    ..The antagonistic action of ecdysone and the conserved insulin/insulin growth factor (IGF) signaling pathway regulate systemic growth and modulate final body size [2, 3]...
  3. Demontis F, Perrimon N. Integration of Insulin receptor/Foxo signaling and dMyc activity during muscle growth regulates body size in Drosophila. Development. 2009;136:983-93 pubmed publisher
    ..Inhibition of Insulin receptor (InR; Insulin-like receptor) signaling in muscles autonomously reduces muscle size and systemically affects ..
  4. Tu M, Yin C, Tatar M. Impaired ovarian ecdysone synthesis of Drosophila melanogaster insulin receptor mutants. Aging Cell. 2002;1:158-60 pubmed
  5. Ueishi S, Shimizu H, H Inoue Y. Male germline stem cell division and spermatocyte growth require insulin signaling in Drosophila. Cell Struct Funct. 2009;34:61-9 pubmed
    ..However, molecular mechanisms inducing division of male GSCs have not been reported. Insulin-like peptides are known to play an essential role in stimulation of proliferation and growth of somatic cells, ..
  6. Stieper B, Kupershtok M, Driscoll M, Shingleton A. Imaginal discs regulate developmental timing in Drosophila melanogaster. Dev Biol. 2008;321:18-26 pubmed publisher
  7. Hong S, Lee K, Kwak S, Kim A, Bai H, Jung M, et al. Minibrain/Dyrk1a regulates food intake through the Sir2-FOXO-sNPF/NPY pathway in Drosophila and mammals. PLoS Genet. 2012;8:e1002857 pubmed publisher
    ..Conversely, AKT-mediated insulin signaling suppressed FOXO-mediated sNPF/NPY expression, which resulted in decreasing food intake...
  8. Nuzhdin S, Brisson J, Pickering A, Wayne M, Harshman L, McIntyre L. Natural genetic variation in transcriptome reflects network structure inferred with major effect mutations: insulin/TOR and associated phenotypes in Drosophila melanogaster. BMC Genomics. 2009;10:124 pubmed publisher
    ..We focus on the latter problem by describing genetic variation in transcript levels of genes in the InR/TOR pathway among 72 Drosophila melanogaster genotypes...
  9. Yang S, Wang W, Chen C, Tseng C, Chen Y, Hsu H. FOXO/Fringe is necessary for maintenance of the germline stem cell niche in response to insulin insufficiency. Dev Biol. 2013;382:124-35 pubmed publisher
    ..However, it is not clear how these signals are merged within the niche. Nutrient-sensing insulin/FOXO signaling has been previously shown to directly control Notch activation in the Drosophila female germline ..

More Information

Publications90

  1. Hyun S, Lee J, Jin H, Nam J, Namkoong B, Lee G, et al. Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K. Cell. 2009;139:1096-108 pubmed publisher
    ..miR-8 null flies are smaller in size and defective in insulin signaling in fat body that is the fly counterpart of liver and adipose tissue...
  2. Broughton S, Alic N, Slack C, Bass T, Ikeya T, Vinti G, et al. Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs. PLoS ONE. 2008;3:e3721 pubmed publisher
    The insulin/IGF-like signalling (IIS) pathway has diverse functions in all multicellular organisms, including determination of lifespan...
  3. Wu Q, Brown M. Signaling and function of insulin-like peptides in insects. Annu Rev Entomol. 2006;51:1-24 pubmed
    b>Insulin-like peptides (ILPs) exist in insects and are encoded by multigene families that are expressed in the brain and other tissues...
  4. Apidianakis Y, Rahme L. Drosophila melanogaster as a model for human intestinal infection and pathology. Dis Model Mech. 2011;4:21-30 pubmed publisher
    ..In this Perspective, we discuss recent advances in the study of Drosophila intestinal infection and pathology, and briefly review the parallels and differences between human and Drosophila intestinal regeneration and disease. ..
  5. Petruzzelli L, Herrera R, Garcia Arenas R, Rosen O. Acquisition of insulin-dependent protein tyrosine kinase activity during Drosophila embryogenesis. J Biol Chem. 1985;260:16072-5 pubmed
    ..conclude that the insulin-binding and insulin-dependent protein tyrosine kinase activities of the mammalian insulin receptor are conserved in Drosophila...
  6. McNeill H, Craig G, Bateman J. Regulation of neurogenesis and epidermal growth factor receptor signaling by the insulin receptor/target of rapamycin pathway in Drosophila. Genetics. 2008;179:843-53 pubmed publisher
    ..We have previously shown that growth and neuronal differentiation are coordinated by the insulin receptor/target of rapamycin (TOR) kinase (InR/TOR) pathway...
  7. Bateman J, McNeill H. Temporal control of differentiation by the insulin receptor/tor pathway in Drosophila. Cell. 2004;119:87-96 pubmed
    ..In a screen for patterning mutants, we isolated alleles of tsc1, a component of the insulin receptor (InR) growth control pathway...
  8. Slack C, Giannakou M, Foley A, Goss M, Partridge L. dFOXO-independent effects of reduced insulin-like signaling in Drosophila. Aging Cell. 2011;10:735-48 pubmed publisher
    The insulin/insulin-like growth factor-like signaling (IIS) pathway in metazoans has evolutionarily conserved roles in growth control, metabolic homeostasis, stress responses, reproduction, and lifespan...
  9. Shim J, Mukherjee T, Banerjee U. Direct sensing of systemic and nutritional signals by haematopoietic progenitors in Drosophila. Nat Cell Biol. 2012;14:394-400 pubmed publisher
    ..Here, we show that the haematopoietic progenitors of Drosophila are direct targets of systemic (insulin) and nutritional (essential amino acid) signals, and that these systemic signals maintain the progenitors by ..
  10. Hsu Y, Chern J, Cai Y, Liu M, Choi K. Drosophila TCTP is essential for growth and proliferation through regulation of dRheb GTPase. Nature. 2007;445:785-8 pubmed
    ..Our studies identify TCTP as a direct regulator of Rheb and a potential therapeutic target for TSC disease. ..
  11. Day S, Lawrence P. Measuring dimensions: the regulation of size and shape. Development. 2000;127:2977-87 pubmed
    ..We discuss a hypothesis that the local steepness of a morphogen gradient is a measure of length in one axis, a measure that is used to determine whether there will be net growth or not. ..
  12. Werz C, Kohler K, Hafen E, Stocker H. The Drosophila SH2B family adaptor Lnk acts in parallel to chico in the insulin signaling pathway. PLoS Genet. 2009;5:e1000596 pubmed publisher
    ..Genetic epistasis analysis places lnk downstream of the insulin receptor (InR) and upstream of phosphoinositide 3-kinase (PI3K) in the IIS cascade, at the same level as chico (..
  13. Garofalo R, Rosen O. Tissue localization of Drosophila melanogaster insulin receptor transcripts during development. Mol Cell Biol. 1988;8:1638-47 pubmed
    The Drosophila melanogaster insulin receptor (Drosophila insulin receptor homolog [dIRH]) is similar to its mammalian counterpart in deduced amino acid sequence, subunit structure, and ligand-stimulated protein tyrosine kinase activity...
  14. Honegger B, Galic M, Kohler K, Wittwer F, Brogiolo W, Hafen E, et al. Imp-L2, a putative homolog of vertebrate IGF-binding protein 7, counteracts insulin signaling in Drosophila and is essential for starvation resistance. J Biol. 2008;7:10 pubmed publisher
    b>Insulin and insulin-like growth factors (IGFs) signal through a highly conserved pathway and control growth and metabolism in both vertebrates and invertebrates...
  15. Puig O, Marr M, Ruhf M, Tjian R. Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway. Genes Dev. 2003;17:2006-20 pubmed
    The Drosophila insulin receptor (dInR) regulates cell growth and proliferation through the dPI3K/dAkt pathway, which is conserved in metazoan organisms...
  16. Helfand S, Rogina B. Molecular genetics of aging in the fly: is this the end of the beginning?. Bioessays. 2003;25:134-41 pubmed
  17. Buch S, Melcher C, Bauer M, Katzenberger J, Pankratz M. Opposing effects of dietary protein and sugar regulate a transcriptional target of Drosophila insulin-like peptide signaling. Cell Metab. 2008;7:321-32 pubmed publisher
    Specific neurosecretory cells of the Drosophila brain express insulin-like peptides (dilps), which regulate growth, glucose homeostasis, and aging...
  18. Gao X, Neufeld T, Pan D. Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways. Dev Biol. 2000;221:404-18 pubmed
    ..Furthermore, we show that dPTEN does not play a major role in cell survival during Drosophila development. Our results provide a potential explanation for the high frequency of PTEN mutation in human cancer. ..
  19. Oldham S, Stocker H, Laffargue M, Wittwer F, Wymann M, Hafen E. The Drosophila insulin/IGF receptor controls growth and size by modulating PtdInsP(3) levels. Development. 2002;129:4103-9 pubmed
    Understanding the control of size is of fundamental biological and clinical importance. Insulin/IGF signaling during development controls growth and size, possibly by coordinating the activities of the Ras and PI 3-kinase signaling ..
  20. Amcheslavsky A, Jiang J, Ip Y. Tissue damage-induced intestinal stem cell division in Drosophila. Cell Stem Cell. 2009;4:49-61 pubmed publisher
    ..By using this newly established system of intestinal stem cell proliferation and tissue regeneration, we find that the insulin receptor signaling pathway is required for intestinal stem cell division.
  21. Slaidina M, Delanoue R, Gronke S, Partridge L, Leopold P. A Drosophila insulin-like peptide promotes growth during nonfeeding states. Dev Cell. 2009;17:874-84 pubmed publisher
    ..availability of nutrients--stored internally or obtained from the environment--and the resulting activation of insulin/IGF signaling (IIS)...
  22. Rera M, Clark R, Walker D. Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc Natl Acad Sci U S A. 2012;109:21528-33 pubmed publisher
    ..in identifying individual flies with systemic metabolic defects previously linked to aging, including impaired insulin/insulin-like growth factor signaling, as evidenced by a reduction in Akt activation and up-regulation of dFOXO ..
  23. Biteau B, Karpac J, Supoyo S, Degennaro M, Lehmann R, Jasper H. Lifespan extension by preserving proliferative homeostasis in Drosophila. PLoS Genet. 2010;6:e1001159 pubmed publisher
    ..These include reduced Insulin/IGF or Jun-N-terminal Kinase (JNK) signaling activities, as well as over-expression of stress-protective genes in ..
  24. Wigby S, Slack C, Gronke S, Martinez P, Calboli F, Chapman T, et al. Insulin signalling regulates remating in female Drosophila. Proc Biol Sci. 2011;278:424-31 pubmed publisher
    ..The evolutionarily conserved insulin/insulin-like growth factor-like signalling (IIS) pathway is responsive to nutrition, and regulates development, ..
  25. Britton J, Lockwood W, Li L, Cohen S, Edgar B. Drosophila's insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions. Dev Cell. 2002;2:239-49 pubmed
    Studies in Drosophila have characterized insulin receptor/phosphoinositide 3-kinase (Inr/PI3K) signaling as a potent regulator of cell growth, but its function during development has remained uncertain...
  26. Mirth C, Truman J, Riddiford L. The role of the prothoracic gland in determining critical weight for metamorphosis in Drosophila melanogaster. Curr Biol. 2005;15:1796-807 pubmed
    ..We present evidence that in Drosophila, a component of the ring gland, the prothoracic gland (PG), assesses growth to determine when critical weight has been achieved...
  27. Belgacem Y, Martin J. Disruption of insulin pathways alters trehalose level and abolishes sexual dimorphism in locomotor activity in Drosophila. J Neurobiol. 2006;66:19-32 pubmed
    ..Moreover, we also show that in the head of adult flies, the insulin receptor (InR) is expressed only in the fat body surrounding the brain...
  28. Zhao X, Campos A. Insulin signalling in mushroom body neurons regulates feeding behaviour in Drosophila larvae. J Exp Biol. 2012;215:2696-702 pubmed publisher
    ..organization of the Drosophila larval brain and the availability of genetic tools to impair the function of insulin receptor signalling in a spatially specific manner makes Drosophila an attractive model to investigate the role of the ..
  29. Brogiolo W, Stocker H, Ikeya T, Rintelen F, Fernandez R, Hafen E. An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Curr Biol. 2001;11:213-21 pubmed
    ..an evolutionarily conserved signaling pathway that regulates organismal size and that includes the Drosophila insulin receptor substrate homolog Chico, the lipid kinase PI(3)K (Dp110), DAkt1/dPKB, and dS6K...
  30. Kenyon C. The plasticity of aging: insights from long-lived mutants. Cell. 2005;120:449-60 pubmed
    ..Many mutations affecting longevity pathways delay age-related disease, and the molecular analysis of these pathways is leading to a mechanistic understanding of how these two processes--aging and disease susceptibility--are linked. ..
  31. Huang H, Potter C, Tao W, Li D, Brogiolo W, Hafen E, et al. PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development. Development. 1999;126:5365-72 pubmed
    ..Furthermore, we have shown that PTEN acts in the insulin signaling pathway and all signals from the insulin receptor can be antagonized by either Drosophila or human PTEN, suggesting a potential means for alleviating symptoms ..
  32. Scott R, Schuldiner O, Neufeld T. Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev Cell. 2004;7:167-78 pubmed
    ..Thus, in cells lacking TOR, autophagy plays a protective role that is dominant over its potential role as a growth suppressor. ..
  33. Tatar M, Kopelman A, Epstein D, Tu M, Yin C, Garofalo R. A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science. 2001;292:107-10 pubmed
    The Drosophila melanogaster gene insulin-like receptor (InR) is homologous to mammalian insulin receptors as well as to Caenorhabditis elegans daf-2, a signal transducer regulating worm dauer formation and adult longevity...
  34. Wittwer F, Jaquenoud M, Brogiolo W, Zarske M, Wüstemann P, Fernandez R, et al. Susi, a negative regulator of Drosophila PI3-kinase. Dev Cell. 2005;8:817-27 pubmed
    ..Here, we describe Susi, a coiled-coil domain protein that acts as a negative regulator of insulin signaling in Drosophila. Whereas loss of Susi function increases body size, overexpression of Susi reduces growth...
  35. Pflieger D, Jünger M, Muller M, Rinner O, Lee H, Gehrig P, et al. Quantitative proteomic analysis of protein complexes: concurrent identification of interactors and their state of phosphorylation. Mol Cell Proteomics. 2008;7:326-46 pubmed
    ..of samples immunopurified from Drosophila melanogaster cells expressing an epitope-tagged form of the insulin receptor substrate homologue Chico...
  36. Mirth C, Truman J, Riddiford L. The ecdysone receptor controls the post-critical weight switch to nutrition-independent differentiation in Drosophila wing imaginal discs. Development. 2009;136:2345-53 pubmed publisher
    ..Previously, we found that reaching critical weight depends on the insulin-dependent growth of the prothoracic glands (PGs) in Drosophila larvae...
  37. Wu Q, Zhang Y, Xu J, Shen P. Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila. Proc Natl Acad Sci U S A. 2005;102:13289-94 pubmed
    ..Here, we report on the function and mechanism of the Drosophila insulin-like system in the central regulation of different hunger-driven behaviors...
  38. Storelli G, Defaye A, Erkosar B, Hols P, Royet J, Leulier F. Lactobacillus plantarum promotes Drosophila systemic growth by modulating hormonal signals through TOR-dependent nutrient sensing. Cell Metab. 2011;14:403-14 pubmed publisher
    ..Our results indicate that the intestinal microbiota should also be envisaged as a factor that influences the systemic growth of its host...
  39. Rintelen F, Stocker H, Thomas G, Hafen E. PDK1 regulates growth through Akt and S6K in Drosophila. Proc Natl Acad Sci U S A. 2001;98:15020-5 pubmed
    The insulin/insulin-like growth factor-1 signaling pathway promotes growth in invertebrates and vertebrates by increasing the levels of phosphatidylinositol 3,4,5-triphosphate through the activation of p110 phosphatidylinositol 3-kinase...
  40. Ikeya T, Broughton S, Alic N, Grandison R, Partridge L. The endosymbiont Wolbachia increases insulin/IGF-like signalling in Drosophila. Proc Biol Sci. 2009;276:3799-807 pubmed publisher
    b>Insulin/IGF-like signalling (IIS) is an evolutionarily conserved pathway that has diverse functions in multi-cellular organisms...
  41. Linneweber G, Jacobson J, Busch K, Hudry B, Christov C, Dormann D, et al. Neuronal control of metabolism through nutrient-dependent modulation of tracheal branching. Cell. 2014;156:69-83 pubmed publisher
    ..distinct populations of nutrient- and oxygen-responsive neurons that, through delivery of both local and systemic insulin- and VIP-like neuropeptides, sculpt the growth of specific tracheal subsets...
  42. Fernandez Almonacid R, Rosen O. Structure and ligand specificity of the Drosophila melanogaster insulin receptor. Mol Cell Biol. 1987;7:2718-27 pubmed
    The insulin-binding and protein tyrosine kinase subunits of the Drosophila melanogaster insulin receptor homolog have been identified and characterized by using antipeptide antibodies elicited to the deduced amino acid sequence of the ..
  43. Giannakou M, Goss M, Jacobson J, Vinti G, Leevers S, Partridge L. Dynamics of the action of dFOXO on adult mortality in Drosophila. Aging Cell. 2007;6:429-38 pubmed
    The insulin/insulin growth factor (IGF)-like signaling (IIS) pathway has a conserved role in regulating lifespan in Caenorhabditis elegans, Drosophila and mice. Extension of lifespan by reduced IIS has been shown in C...
  44. Belgacem Y, Martin J. Hmgcr in the corpus allatum controls sexual dimorphism of locomotor activity and body size via the insulin pathway in Drosophila. PLoS ONE. 2007;2:e187 pubmed
    ..In Drosophila, mutations in the insulin receptor (InR) decrease the rate of JH synthesis...
  45. Yenush L, Fernandez R, Myers M, Grammer T, Sun X, Blenis J, et al. The Drosophila insulin receptor activates multiple signaling pathways but requires insulin receptor substrate proteins for DNA synthesis. Mol Cell Biol. 1996;16:2509-17 pubmed
    The Drosophila insulin receptor (DIR) contains a 368-amino-acid COOH-terminal extension that contains several tyrosine phosphorylation sites in YXXM motifs...
  46. Potter C, Huang H, Xu T. Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell. 2001;105:357-68 pubmed
    ..Genetic epistasis data are consistent with a model that Tsc1 and Tsc2 function together in the insulin signaling pathway.
  47. Partridge L, Gems D, Withers D. Sex and death: what is the connection?. Cell. 2005;120:461-72 pubmed
    ..Mutations in insulin/IGF signaling (IIS) pathways and dietary restriction (DR) can extend lifespan in model organisms but do not ..
  48. Sousa Nunes R, Yee L, Gould A. Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila. Nature. 2011;471:508-12 pubmed publisher
    ..Downstream of this signal, Insulin-like receptor signalling and the Phosphatidylinositol 3-kinase (PI3K)/TOR network are required in neuroblasts for ..
  49. O Farrell F, Wang S, Katheder N, Rusten T, Samakovlis C. Two-tiered control of epithelial growth and autophagy by the insulin receptor and the ret-like receptor, stitcher. PLoS Biol. 2013;11:e1001612 pubmed publisher
    ..Both Stit and insulin receptor (InR) signaling activate PI3K-I and drive cellular proliferation and tissue growth...
  50. Fernandez R, Tabarini D, Azpiazu N, Frasch M, Schlessinger J. The Drosophila insulin receptor homolog: a gene essential for embryonic development encodes two receptor isoforms with different signaling potential. EMBO J. 1995;14:3373-84 pubmed
    We report the cloning and primary structure of the Drosophila insulin receptor gene (inr), functional expression of the predicted polypeptide, and the isolation of mutations in the inr locus...
  51. Cheng L, Bailey A, Leevers S, Ragan T, Driscoll P, Gould A. Anaplastic lymphoma kinase spares organ growth during nutrient restriction in Drosophila. Cell. 2011;146:435-47 pubmed publisher
    ..kinase (Alk) efficiently protects neural progenitor (neuroblast) growth against reductions in amino acids and insulin-like peptides during NR via two mechanisms...
  52. Jünger M, Rintelen F, Stocker H, Wasserman J, Végh M, Radimerski T, et al. The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J Biol. 2003;2:20 pubmed
    ..belonging to the FOXO subfamily are negatively regulated by protein kinase B (PKB) in response to signaling by insulin and insulin-like growth factor in Caenorhabditis elegans and mammals...
  53. Zhang W, Thompson B, Hietakangas V, Cohen S. MAPK/ERK signaling regulates insulin sensitivity to control glucose metabolism in Drosophila. PLoS Genet. 2011;7:e1002429 pubmed publisher
    The insulin/IGF-activated AKT signaling pathway plays a crucial role in regulating tissue growth and metabolism in multicellular animals...
  54. Tang H, Smith Caldas M, Driscoll M, Salhadar S, Shingleton A. FOXO regulates organ-specific phenotypic plasticity in Drosophila. PLoS Genet. 2011;7:e1002373 pubmed publisher
    ..In all animals, developmental nutrition is signaled to growing organs via the insulin-signaling pathway...
  55. Gao X, Pan D. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev. 2001;15:1383-92 pubmed
    ..strikingly, the heterozygosity of TSC1 or TSC2 is sufficient to rescue the lethality of loss-of-function insulin receptor mutants...
  56. Hsu H, Drummond Barbosa D. Insulin signals control the competence of the Drosophila female germline stem cell niche to respond to Notch ligands. Dev Biol. 2011;350:290-300 pubmed publisher
    ..We previously showed that insulin signals directly stimulate germline stem cell (GSC) division and indirectly promote GSC maintenance via the niche ..
  57. Luo X, Puig O, Hyun J, Bohmann D, Jasper H. Foxo and Fos regulate the decision between cell death and survival in response to UV irradiation. EMBO J. 2007;26:380-90 pubmed
    ..These data suggest that integrating stress and survival signals through Foxo drives the decision between cell death and repair of damaged cells in vivo. ..
  58. Clancy D, Gems D, Harshman L, Oldham S, Stocker H, Hafen E, et al. Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science. 2001;292:104-6 pubmed
    The Drosophila melanogaster gene chico encodes an insulin receptor substrate that functions in an insulin/insulin-like growth factor (IGF) signaling pathway...
  59. Wessells R, Fitzgerald E, Cypser J, Tatar M, Bodmer R. Insulin regulation of heart function in aging fruit flies. Nat Genet. 2004;36:1275-81 pubmed
    b>Insulin-IGF receptor (InR) signaling has a conserved role in regulating lifespan, but little is known about the genetic control of declining organ function...
  60. Grewal S. Controlling animal growth and body size - does fruit fly physiology point the way?. F1000 Biol Rep. 2012;4:12 pubmed publisher
    ..While this concept is obviously not new, these fly studies now open up the possibility of using a genetically tractable system to dissect in detail how organ-to-organ communication dictates body size. ..
  61. Oldham S, Hafen E. Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol. 2003;13:79-85 pubmed
    ..One major orchestrator of this complex growth process in diverse metazoan species is the insulin/insulin-like growth factor (IGF) system...
  62. LaFever L, Feoktistov A, Hsu H, Drummond Barbosa D. Specific roles of Target of rapamycin in the control of stem cells and their progeny in the Drosophila ovary. Development. 2010;137:2117-26 pubmed publisher
    ..showed that germline stem cells (GSCs) and follicle stem cells (FSCs) in the Drosophila ovary respond to diet via insulin signals...
  63. Kockel L, Kerr K, Melnick M, Brückner K, Hebrok M, Perrimon N. Dynamic switch of negative feedback regulation in Drosophila Akt-TOR signaling. PLoS Genet. 2010;6:e1000990 pubmed publisher
    Akt represents a nodal point between the Insulin receptor and TOR signaling, and its activation by phosphorylation controls cell proliferation, cell size, and metabolism...
  64. Bohni R, Riesgo Escovar J, Oldham S, Brogiolo W, Stocker H, Andruss B, et al. Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell. 1999;97:865-75 pubmed
    ..The similarities of the growth defects caused by mutations in chico and the insulin receptor gene in Drosophila and by perturbations of the insulin/IGF1 signaling pathway in vertebrates suggest that ..
  65. Wu Q, Zhao Z, Shen P. Regulation of aversion to noxious food by Drosophila neuropeptide Y- and insulin-like systems. Nat Neurosci. 2005;8:1350-5 pubmed
    ..Moreover, NPFR1 neuronal activity may be directly regulated by the insulin-like signaling pathway...
  66. Siegrist S, Haque N, Chen C, Hay B, Hariharan I. Inactivation of both Foxo and reaper promotes long-term adult neurogenesis in Drosophila. Curr Biol. 2010;20:643-8 pubmed publisher
    ..Prior to their elimination, their growth and proliferation slows because of decreased insulin/PI3 kinase signaling, resulting in nuclear localization of Foxo...
  67. Rideout E, Marshall L, Grewal S. Drosophila RNA polymerase III repressor Maf1 controls body size and developmental timing by modulating tRNAiMet synthesis and systemic insulin signaling. Proc Natl Acad Sci U S A. 2012;109:1139-44 pubmed publisher
    ..Inhibiting Maf1 in the fat body increases growth by promoting the expression of brain-derived insulin-like peptides and consequently enhanced systemic insulin signaling...
  68. Karpac J, Biteau B, Jasper H. Misregulation of an adaptive metabolic response contributes to the age-related disruption of lipid homeostasis in Drosophila. Cell Rep. 2013;4:1250-61 pubmed publisher
    ..We find that activation of the insulin-responsive transcription factor Foxo in intestinal enterocytes is required to inhibit the expression of ..
  69. Papatheodorou I, Ziehm M, Wieser D, Alic N, Partridge L, Thornton J. Using answer set programming to integrate RNA expression with signalling pathway information to infer how mutations affect ageing. PLoS ONE. 2012;7:e50881 pubmed publisher
    ..Answer Set Programming, and use it to infer signalling effects of genetic perturbations, based on a model of the insulin signalling pathway...
  70. Hsu H, Drummond Barbosa D. Insulin levels control female germline stem cell maintenance via the niche in Drosophila. Proc Natl Acad Sci U S A. 2009;106:1117-21 pubmed publisher
    ..Here, we show that insulin signaling integrates the effects of diet and age on germline stem cell (GSC) maintenance through the dual ..
  71. Flatt T, Tu M, Tatar M. Hormonal pleiotropy and the juvenile hormone regulation of Drosophila development and life history. Bioessays. 2005;27:999-1010 pubmed
    ..In particular, we illustrate the role of JH as a key mediator of life history trade-offs. ..
  72. Corl A, Rodan A, Heberlein U. Insulin signaling in the nervous system regulates ethanol intoxication in Drosophila melanogaster. Nat Neurosci. 2005;8:18-9 pubmed
    The insulin signaling pathway regulates multiple physiological processes, including energy metabolism, organismal growth, aging and reproduction...
  73. Grandison R, Piper M, Partridge L. Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature. 2009;462:1061-4 pubmed publisher
    ..Reduced activity of the insulin/insulin-like growth factor signalling pathway extends lifespan in diverse organisms, and we find that it also ..
  74. Coffman C, Wayne M, Nuzhdin S, Higgins L, McIntyre L. Identification of co-regulated transcripts affecting male body size in Drosophila. Genome Biol. 2005;6:R53 pubmed
    ..Applied to body size in Drosophila simulans, an evolutionarily important complex trait, a factor was directly associated with body size. ..
  75. Song J, Wu L, Chen Z, Kohanski R, Pick L. Axons guided by insulin receptor in Drosophila visual system. Science. 2003;300:502-5 pubmed
    ..Here we show that the insulin receptor functions in axon guidance. The Drosophila insulin receptor (DInR) is required for photoreceptor-cell (R-cell) axons to find their way from the retina to the brain ..
  76. Martín Peña A, Acebes A, Rodriguez J, Sorribes A, de Polavieja G, Fernandez Funez P, et al. Age-independent synaptogenesis by phosphoinositide 3 kinase. J Neurosci. 2006;26:10199-208 pubmed
    ..Thus, we propose that PI3K stimulation can be applied to prevent or delay synapse loss in normal aging and in neurological disorders. ..
  77. Chell J, Brand A. Nutrition-responsive glia control exit of neural stem cells from quiescence. Cell. 2010;143:1161-73 pubmed publisher
    ..We have identified a population of glial cells that produce insulin/IGF-like peptides in response to nutrition, and we show that the insulin/IGF receptor pathway is necessary for ..
  78. Lee J, Overstreet E, Fitch E, Fleenor S, Fischer J. Drosophila liquid facets-Related encodes Golgi epsin and is an essential gene required for cell proliferation, growth, and patterning. Dev Biol. 2009;331:1-13 pubmed publisher
    ..In addition, primarily by analyzing mutant eye discs, we found that lqfR is required for cell proliferation, insulin-independent cell growth, and cell patterning, consistent with a role in one or several signaling pathways...
  79. Willecke M, Toggweiler J, Basler K. Loss of PI3K blocks cell-cycle progression in a Drosophila tumor model. Oncogene. 2011;30:4067-74 pubmed publisher
    ..The results presented here broaden our insights into the intricate mechanisms underling tumorigenesis and illustrate the power of Drosophila genetics in revealing weak points of tumor progression. ..
  80. Hsu H, LaFever L, Drummond Barbosa D. Diet controls normal and tumorous germline stem cells via insulin-dependent and -independent mechanisms in Drosophila. Dev Biol. 2008;313:700-12 pubmed
    ..Our previous work showed that germline stem cells (GSCs) respond to diet via neural insulin-like peptides (DILPs) that act directly on the germ line to upregulate stem cell division and cyst growth under a ..
  81. Chen C, Jack J, Garofalo R. The Drosophila insulin receptor is required for normal growth. Endocrinology. 1996;137:846-56 pubmed
    Drosophila contain an insulin receptor homologue, encoded by the inr gene located at position 93E4-5 on the third chromosome...