Gene Symbol: Ilp6
Description: Insulin-like peptide 6
Alias: CG14049, DILP, DILP-6, DILP6, Dilp, Dilp 6, Dilp6, Dmel\CG14049, Ilp, Ilp-6, dILP6, dIlp6, dilp, dilp-6, dilp6, ilp6, Insulin-like peptide 6, CG14049-PA, CG14049-PB, CG14049-PC, CG14049-PD, Ilp6-PA, Ilp6-PB, Ilp6-PC, Ilp6-PD, drosophila insulin-like peptide 6, insulin-like peptide, insulin-like peptide 6
Species: fruit fly

Top Publications

  1. 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. ..
  2. 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
    ..This review summarizes current studies primarily from Drosophila regarding the function of the insulin/IGF system in the control of growth. ..
  3. 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
    ..Drosophila thus contains two segregated ILP pools, one regulating proliferation within the central nervous system and the other controlling tissue growth ..
  4. 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
    ..This study shows that the Drosophila insulin receptor autonomously controls cell and organ size, and that overexpression of a gene encoding an insulin-like peptide is sufficient to increase body size. ..
  5. Ikeya T, Galic M, Belawat P, Nairz K, Hafen E. Nutrient-dependent expression of insulin-like peptides from neuroendocrine cells in the CNS contributes to growth regulation in Drosophila. Curr Biol. 2002;12:1293-300 pubmed
    ..Three of the dilp genes are expressed in seven median neurosecretory cells (m-NSCs) in the brain...
  6. Hwangbo D, Gershman B, Gersham B, Tu M, Palmer M, Tatar M. Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature. 2004;429:562-6 pubmed
    ..We further show that this limited activation of dFOXO reduces expression of the Drosophila insulin-like peptide dilp-2 synthesized in neurons, and represses endogenous insulin-dependent signalling in peripheral fat body...
  7. Chell J, Brand A. Nutrition-responsive glia control exit of neural stem cells from quiescence. Cell. 2010;143:1161-73 pubmed publisher
  8. Wu Q, Brown M. Signaling and function of insulin-like peptides in insects. Annu Rev Entomol. 2006;51:1-24 pubmed
    ..a) an integrated summary of the efforts to characterize the distribution of ILPs in insects and to define this pathway and its functions in Drosophila and (b) a few considerations for future studies of ILP endocrinology in insects.
  9. Teleman A. Molecular mechanisms of metabolic regulation by insulin in Drosophila. Biochem J. 2009;425:13-26 pubmed publisher
    ..I discuss both the intracellular signalling network, as well as the communication between organs in the fly. ..

More Information


  1. Okamoto N, Yamanaka N, Yagi Y, Nishida Y, Kataoka H, O Connor M, et al. A fat body-derived IGF-like peptide regulates postfeeding growth in Drosophila. Dev Cell. 2009;17:885-91 pubmed publisher
    ..Here we show that Drosophila insulin-like peptide 6 (DILP6), which is structurally similar to vertebrate insulin-like growth factor (IGF), is predominantly expressed in the ..
  2. Zhang H, Liu J, Li C, Momen B, Kohanski R, Pick L. Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities. Proc Natl Acad Sci U S A. 2009;106:19617-22 pubmed publisher
    ..In contrast, Df[dilp6] or Df[dilp7] animals showed no major metabolic defects...
  3. Gronke S, Clarke D, Broughton S, Andrews T, Partridge L. Molecular evolution and functional characterization of Drosophila insulin-like peptides. PLoS Genet. 2010;6:e1000857 pubmed publisher
    ..notably with DILP3 required for normal expression of DILPs 2 and 5 in brain neurosecretory cells and expression of DILP6 in the fat body compensating for loss of brain DILPs...
  4. 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
    ..We show here that, during metamorphosis, when feeding stops, a specific DILP (Dilp6) is produced by the fat body and relays the growth signal...
  5. Bai H, Kang P, Tatar M. Drosophila insulin-like peptide-6 (dilp6) expression from fat body extends lifespan and represses secretion of Drosophila insulin-like peptide-2 from the brain. Aging Cell. 2012;11:978-85 pubmed publisher
    ..Here, we show that the insulin-regulated transcription factor dFOXO positively modulates dilp6 mRNA in adult fat body...
  6. 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
    ..Our methods are available in the web-service NetEffects: ..
  7. Libert S. Insights into physiology of aging and novel ways to increase lifespan. Fly (Austin). 2007;1:113-5 pubmed
  8. Guirao Rico S, Aguade M. Molecular evolution of the ligands of the insulin-signaling pathway: dilp genes in the genus Drosophila. Mol Biol Evol. 2011;28:1557-60 pubmed publisher
  9. Aradhya R, Zmojdzian M, Da Ponte J, Jagla K. Muscle niche-driven Insulin-Notch-Myc cascade reactivates dormant Adult Muscle Precursors in Drosophila. elife. 2015;4: pubmed publisher
    ..Indeed, our genetic analyses indicate that muscles send inductive dIlp6 signals that switch the Insulin pathway ON in closely associated AMPs...
  10. Avet Rochex A, Kaul A, Gatt A, McNeill H, Bateman J. Concerted control of gliogenesis by InR/TOR and FGF signalling in the Drosophila post-embryonic brain. Development. 2012;139:2763-72 pubmed publisher
    ..In summary, we have identified two major pathways that control perineural and cortex gliogenesis in the post-embryonic brain and have shown that the molecular circuitry required is lineage specific. ..
  11. Liu J, Spéder P, Brand A. Control of brain development and homeostasis by local and systemic insulin signalling. Diabetes Obes Metab. 2014;16 Suppl 1:16-20 pubmed publisher
    ..In addition, we describe how local insulin/IGF signalling couples neural stem cell proliferation with systemic energy state in Drosophila and in mammals. ..
  12. Chatterjee D, Katewa S, Qi Y, Jackson S, Kapahi P, Jasper H. Control of metabolic adaptation to fasting by dILP6-induced insulin signaling in Drosophila oenocytes. Proc Natl Acad Sci U S A. 2014;111:17959-64 pubmed publisher
    ..Furthermore, we find that fat body-derived Drosophila insulin-like peptide 6 (dILP6) induces lipid uptake in oenocytes, promoting lipid turnover during fasting and increasing starvation tolerance of ..
  13. Vandersmissen H, Van Hiel M, Van Loy T, Vleugels R, Vanden Broeck J. Silencing D. melanogaster lgr1 impairs transition from larval to pupal stage. Gen Comp Endocrinol. 2014;209:135-47 pubmed publisher
  14. Ismail M, Hodges M, Boylan M, Achall R, Shirras A, Broughton S. The Drosophila insulin receptor independently modulates lifespan and locomotor senescence. PLoS ONE. 2015;10:e0125312 pubmed publisher
  15. Gu T, Zhao T, Hewes R. Insulin signaling regulates neurite growth during metamorphic neuronal remodeling. Biol Open. 2014;3:81-93 pubmed publisher
    ..Moreover, they highlight strong evolutionarily conservation of insulin signaling in neuronal growth regulation. ..
  16. Wang L, McLeod C, Jones D. Regulation of adult stem cell behavior by nutrient signaling. Cell Cycle. 2011;10:2628-34 pubmed
    ..Here we discuss our data regarding the effects and mechanisms by which changes in systemic nutritional conditions may influence the maintenance and activity of adult stem cells via insulin signaling. ..
  17. Liu Y, Liao S, Veenstra J, Nässel D. Drosophila insulin-like peptide 1 (DILP1) is transiently expressed during non-feeding stages and reproductive dormancy. Sci Rep. 2016;6:26620 pubmed publisher
    ..The dilp1 mRNA level is increased in dilp2, 3, 5 and dilp6 mutant flies, indicating feedback regulation...
  18. Cao H, Wiemerslage L, Marttila P, Williams M, Schiöth H. Bis-(2-ethylhexyl) Phthalate Increases Insulin Expression and Lipid Levels in Drosophila melanogaster. Basic Clin Pharmacol Toxicol. 2016;119:309-16 pubmed publisher
    ..Our results suggest that long-term DEHP feeding may induce diabetes-like dysfunctions. These findings provide a molecular background of how DEHP may have detrimental effects on metabolic functions. ..
  19. Kim J, Bang H, Ko S, Jung I, Hong H, Kim Ha J. Drosophila ia2 modulates secretion of insulin-like peptide. Comp Biochem Physiol A Mol Integr Physiol. 2008;151:180-4 pubmed publisher
    ..As the pancreas develops from the gut during vertebrate development, our results suggest a possible role of IA-2 in insulin and hexokinase regulation. ..
  20. Williams M, Perland E, Eriksson M, Carlsson J, Erlandsson D, Laan L, et al. Recurrent Sleep Fragmentation Induces Insulin and Neuroprotective Mechanisms in Middle-Aged Flies. Front Aging Neurosci. 2016;8:180 pubmed publisher
    ..The fact that neuroprotective pathways remain upregulated in middle-aged flies beyond sleep fragmentation suggests it might represent a strong stressor for the brain during later life. ..
  21. Spéder P, Brand A. Gap junction proteins in the blood-brain barrier control nutrient-dependent reactivation of Drosophila neural stem cells. Dev Cell. 2014;30:309-21 pubmed publisher
    ..We propose that gap junctions in the blood-brain barrier are required to translate metabolic signals into synchronized calcium pulses and insulin secretion. ..
  22. Claeys I, Simonet G, Poels J, Van Loy T, Vercammen L, De Loof A, et al. Insulin-related peptides and their conserved signal transduction pathway. Peptides. 2002;23:807-16 pubmed
  23. Yamamoto R, Bai H, Dolezal A, Amdam G, Tatar M. Juvenile hormone regulation of Drosophila aging. BMC Biol. 2013;11:85 pubmed publisher
    ..We identify transcripts that change in response to juvenile hormone independent of reproductive state and suggest these represent somatically expressed genes that could modulate how juvenile hormone controls persistence and longevity. ..
  24. Ostojic I, Boll W, Waterson M, Chan T, Chandra R, Pletcher S, et al. Positive and negative gustatory inputs affect Drosophila lifespan partly in parallel to dFOXO signaling. Proc Natl Acad Sci U S A. 2014;111:8143-8 pubmed publisher
    ..Together our data suggest that different gustatory cues can modulate the activities of distinct signaling pathways, including different insulin-like peptides, to promote physiological changes that ultimately affect lifespan. ..
  25. Okamoto N, Nakamori R, Murai T, Yamauchi Y, Masuda A, Nishimura T. A secreted decoy of InR antagonizes insulin/IGF signaling to restrict body growth in Drosophila. Genes Dev. 2013;27:87-97 pubmed publisher
    ..We propose that Drosophila uses a secreted decoy to fine-tune systemic growth against fluctuations of circulating insulin levels. ..
  26. Matsuda H, Yamada T, Yoshida M, Nishimura T. Flies without trehalose. J Biol Chem. 2015;290:1244-55 pubmed publisher
    ..These diet-dependent phenotypes of Tps1 mutants demonstrate the critical role of trehalose during development in Drosophila and reveal how animals adapt to changes in nutrient availability. ..
  27. Shingleton A. Body-size regulation: combining genetics and physiology. Curr Biol. 2005;15:R825-7 pubmed
    ..New research has revealed that the activity of the insulin-signaling pathway in the prothoracic gland of Drosophila modulates ecdysone release and thereby influences both the duration and rate of larval growth. ..
  28. McClure K, French R, Heberlein U. A Drosophila model for fetal alcohol syndrome disorders: role for the insulin pathway. Dis Model Mech. 2011;4:335-46 pubmed publisher
    ..due to the effects of ethanol on insulin signaling; specifically, a reduction in Drosophila insulin-like peptide (Dilp) and insulin receptor expression...
  29. Guirao Rico S, Aguade M. Patterns of nucleotide diversity at the regions encompassing the Drosophila insulin-like peptide (dilp) genes: demography vs. positive selection in Drosophila melanogaster. PLoS ONE. 2013;8:e53593 pubmed publisher
    ..melanogaster has provided some evidence for the action of positive selection at or near these genes. The regions encompassing the dilp1-4 genes and the dilp6 gene stand out as likely affected by recent adaptive events.
  30. 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. ..
  31. Bradley G, Leevers S. Amino acids and the humoral regulation of growth: fat bodies use slimfast. Cell. 2003;114:656-8 pubmed
    ..In this issue of Cell, Colombani et al. demonstrate that amino acid-responsive TOR signaling in the Drosophila fat body modulates insulin signaling and growth in peripheral tissues. ..
  32. Lee G, Jun J, Hyun S. MicroRNA miR-8 regulates multiple growth factor hormones produced from Drosophila fat cells. Insect Mol Biol. 2015;24:311-8 pubmed publisher
    ..Drosophila insulin-like peptide 6 (Dilp6) and imaginal morphogenesis protein-late 2 (Imp-L2), a binding partner of Dilp, are also up-regulated in the fat ..
  33. Chen Q, Das S, Visic P, Buford K, Zong Y, Buti W, et al. The drosophila T-box transcription factor midline functions within Insulin/Akt and c-Jun-N terminal kinase stress-reactive signaling pathways to regulate interommatial bristle formation and cell survival. Mech Dev. 2015;136:8-29 pubmed publisher
  34. Min S, Chae H, Jang Y, Choi S, Lee S, Jeong Y, et al. Identification of a Peptidergic Pathway Critical to Satiety Responses in Drosophila. Curr Biol. 2016;26:814-20 pubmed publisher
    ..Together, our results reveal a novel anorexigenic pathway that controls satiety in Drosophila and provide a new avenue to study how the brain actively maintains a constant BW. ..
  35. Sano H, Nakamura A, Texada M, Truman J, Ishimoto H, Kamikouchi A, et al. The Nutrient-Responsive Hormone CCHamide-2 Controls Growth by Regulating Insulin-like Peptides in the Brain of Drosophila melanogaster. PLoS Genet. 2015;11:e1005209 pubmed publisher
    ..Our genetic approach in Drosophila melanogaster provides the first evidence, to our knowledge, that bombesin receptor signaling with its endogenous ligand promotes insulin production. ..
  36. Abholz E, Adonyeva N, Gruntenko N, Rauschenbach I. [Gene dilp6 regulates octopamine metabolism in Drosophila melanogaster]. Genetika. 2016;52:718-22 pubmed
    The effect of strong hypomorphic mutation of the insulin-like protein gene (dilp6) on metabolism of octopamine (one of the main biogenic amines in insects) was studied in Drosophila melanogaster males and females...
  37. Partridge L, Alic N, Bjedov I, Piper M. Ageing in Drosophila: the role of the insulin/Igf and TOR signalling network. Exp Gerontol. 2011;46:376-81 pubmed publisher
    ..Reduced IIS can act acutely to lower death rate, implying that it may ameliorate the effects of ageing-related damage, rather than preventing it. ..
  38. Okamoto N, Nishimura T. Signaling from Glia and Cholinergic Neurons Controls Nutrient-Dependent Production of an Insulin-like Peptide for Drosophila Body Growth. Dev Cell. 2015;35:295-310 pubmed publisher
    ..Glia-derived Dilp6 remotely regulates the FoxO activity in IPCs, primarily through Jeb secreted by cholinergic neurons...
  39. Kelsey E, Luo X, Brückner K, Jasper H. Schnurri regulates hemocyte function to promote tissue recovery after DNA damage. J Cell Sci. 2012;125:1393-400 pubmed publisher
    ..Our results identify a new Shn-regulated paracrine signaling interaction between damaged retinal cells and hemocytes that ensures recovery and homeostasis of the challenged tissue. ..
  40. Parisi F, Riccardo S, Zola S, Lora C, Grifoni D, Brown L, et al. dMyc expression in the fat body affects DILP2 release and increases the expression of the fat desaturase Desat1 resulting in organismal growth. Dev Biol. 2013;379:64-75 pubmed publisher
    ..In addition, the regulation of Desat1 controls the synthesis of triglycerides in FB and this may affect the humoral signal that controls DILP2 release in the brain. ..
  41. Banerjee K, Ayyub C, Sengupta S, Kolthur Seetharam U. dSir2 deficiency in the fatbody, but not muscles, affects systemic insulin signaling, fat mobilization and starvation survival in flies. Aging (Albany NY). 2012;4:206-23 pubmed
    ..In conclusion, these findings highlight the central role that fatbody dSir2 plays in linking metabolism to organismal physiology and its importance for survival...
  42. Williams M, Eriksson A, Shaik M, Voisin S, Yamskova O, Paulsson J, et al. The Obesity-Linked Gene Nudt3 Drosophila Homolog Aps Is Associated With Insulin Signaling. Mol Endocrinol. 2015;29:1303-19 pubmed publisher
    ..Finally, the loss of IPC Aps lowered the expression of Akh, Ilp6, and Ilp3, genes known to be inhibited by insulin signaling...
  43. Post S, Tatar M. Nutritional Geometric Profiles of Insulin/IGF Expression in Drosophila melanogaster. PLoS ONE. 2016;11:e0155628 pubmed publisher
    ..To understand how dietary protein and sugar affect dilp expression, we followed the analytical concepts of the Nutritional Geometric Framework, feeding Drosophila adults ..
  44. Rauschenbach I, Karpova E, Burdina E, Adonyeva N, Bykov R, Ilinsky Y, et al. Insulin-like peptide DILP6 regulates juvenile hormone and dopamine metabolism in Drosophila females. Gen Comp Endocrinol. 2017;243:1-9 pubmed publisher
    Insulin-like peptide DILP6 is a component of the insulin/insulin-like growth factor signalling pathway of Drosophila. Juvenile hormone (JH) and dopamine (DA) are involved in the stress response and in the control of reproduction...