Genomes and Genes
Gene Symbol: Ilp2
Description: Insulin-like peptide 2
Alias: CG8167, DILP, DILP-2, DILP2, Dilp, Dilp 2, Dilp-2, Dilp2, Dmel\CG8167, ILP2, IRP, Ilp, Ilp-2, dILP-2, dILP2, dIlp2, dilp, dilp-2, dilp2, ilp2, Insulin-like peptide 2, CG8167-PA, Ilp2-PA, Insulin- related peptide 2, Insulin-related peptide, drosophila insulin like peptide 2, drosophila insulin-like peptide 2, insulin-like 2, insulin-like peptide, insulin-like peptide-2
Species: fruit fly
- 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..g., a less accessible solid food). Moreover, up-regulation of Drosophila p70/S6 kinase activity in DILP neurons led to attenuated hunger response by fasted larvae, whereas its down-regulation triggered fed larvae to ..
- Cao C, Brown M. Localization of an insulin-like peptide in brains of two flies. Cell Tissue Res. 2001;304:317-21 pubmed..aegypti females. These specific localizations substantiate the existence of an endogenous insulin-like peptide in Drosophila and suggest that a similar peptide is present in the distantly related mosquitoes. ..
- Nielsen M, Luo X, Biteau B, Syverson K, Jasper H. 14-3-3 Epsilon antagonizes FoxO to control growth, apoptosis and longevity in Drosophila. Aging Cell. 2008;7:688-99 pubmed publisher..Our results further show that increased expression of 14-3-3epsilon reverts FoxO-induced growth defects. 14-3-3epsilon thus serves as a central modulator of FoxO activity in the regulation of growth, cell death and longevity in vivo. ..
- 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..We show that in addition to the Drosophila insulin-like peptide 2 (dilp2) gene, overexpression of dilp1 and dilp3-7 is sufficient to promote growth...
- Birse R, Söderberg J, Luo J, Winther A, Nassel D. Regulation of insulin-producing cells in the adult Drosophila brain via the tachykinin peptide receptor DTKR. J Exp Biol. 2011;214:4201-8 pubmed publisher..b>Dilp2 and Dilp3, but not Dilp5, transcripts were significantly affected by DTKR knockdown in IPCs, both in fed and ..
- Kaplan D, Zimmermann G, Suyama K, Meyer T, Scott M. A nucleostemin family GTPase, NS3, acts in serotonergic neurons to regulate insulin signaling and control body size. Genes Dev. 2008;22:1877-93 pubmed publisher..Peripheral insulin pathway activation rescues the growth defects of ns3 mutants. The findings suggest that NS3 acts in serotonergic neurons to regulate insulin signaling and thus exert global growth control. ..
- O Brien L, Soliman S, Li X, Bilder D. Altered modes of stem cell division drive adaptive intestinal growth. Cell. 2011;147:603-14 pubmed publisher..Thus, tissue renewal programs are not committed to maintain cellular equilibrium; stem cells can remodel organs in response to physiological triggers. ..
- Luo J, Becnel J, Nichols C, Nassel D. Insulin-producing cells in the brain of adult Drosophila are regulated by the serotonin 5-HT1A receptor. Cell Mol Life Sci. 2012;69:471-84 pubmed publisher..In Drosophila, there are seven insulin-like peptides (DILP1-7). Three of these (DILP2, 3 and 5) are produced in median neurosecretory cells of the brain, designated IPCs...
- 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..Our results suggest that the coordinated activities of the conserved NPY- and insulin-like receptor signaling systems are essential for the dynamic regulation of noxious food intake according to the animal's energy state. ..
- 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 decreased mortality and increased lifespan of dFOXO overexpressing flies was uncoupled from any effect on female fecundity and from expression levels of Drosophila insulin-like peptides in the brain. ..
- 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..These findings suggest the stimulation of tRNA(i)(Met) synthesis via inhibition of dMaf1 is limiting for nutrition-dependent growth during development. ..
- Rajan A, Perrimon N. Drosophila cytokine unpaired 2 regulates physiological homeostasis by remotely controlling insulin secretion. Cell. 2012;151:123-37 pubmed publisher..b>Dilp secretion in turn regulates energy balance and promotes systemic growth...
- Birse R, Choi J, Reardon K, Rodriguez J, Graham S, Diop S, et al. High-fat-diet-induced obesity and heart dysfunction are regulated by the TOR pathway in Drosophila. Cell Metab. 2010;12:533-44 pubmed publisher..We conclude that deregulation of insulin-TOR signaling due to a HFD is responsible for mediating the detrimental effects on metabolism and heart function. ..
- Sekine O, Love D, Rubenstein D, Hanover J. Blocking O-linked GlcNAc cycling in Drosophila insulin-producing cells perturbs glucose-insulin homeostasis. J Biol Chem. 2010;285:38684-91 pubmed publisher..Knockdown of Ogt decreased Dilp2, Dilp3, and Dilp5 production, with reduced body size and decreased phosphorylation of Akt in vivo...
- 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..Together, these findings identify a brain-sparing mechanism that shares some regulatory features with the starvation-resistant growth programs of mammalian tumors. ..
- Broughton S, Piper M, Ikeya T, Bass T, Jacobson J, Driege Y, et al. Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc Natl Acad Sci U S A. 2005;102:3105-10 pubmed..However, the ablated flies show an extension of median and maximal lifespan and increased resistance to oxidative stress and starvation. ..
- 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..These data indicate that DILP6 is a functional, as well as a structural, counterpart of vertebrate IGFs. Our data provide in vivo evidence for a role of ILPs in determining adult body size through the regulation of postfeeding growth...
- Karpac J, Hull Thompson J, Falleur M, Jasper H. JNK signaling in insulin-producing cells is required for adaptive responses to stress in Drosophila. Aging Cell. 2009;8:288-95 pubmed publisher..is shown that JNK activity in IPCs of flies is required for oxidative stress-induced repression of the Drosophila ILP2. It is found that this repression is required for growth adaptation to heat stress as well as adult oxidative ..
- 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..These findings suggest a previously unknown role for this highly conserved pathway in regulating the behavioral responses to an addictive drug. ..
- 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. ..
- 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..These results underscore the importance of systemic factors for the regulation of stem cell niches and, thereby, of stem cell numbers. ..
- 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..Thus, we describe a novel mechanism by which nutritional cues modulate neuronal activity to give rise to organ-specific, long-lasting changes in vascular architecture. ..
- Haselton A, Sharmin E, Schrader J, Sah M, Poon P, Fridell Y. Partial ablation of adult Drosophila insulin-producing neurons modulates glucose homeostasis and extends life span without insulin resistance. Cell Cycle. 2010;9:3063-71 pubmed publisher..set out to determine the impact of adult-specific partial ablation of IPCs (IPC knockdown) on insulin-like peptide (ILP) action, metabolic outcomes and longevity...
- Broughton S, Slack C, Alic N, Metaxakis A, Bass T, Driege Y, et al. DILP-producing median neurosecretory cells in the Drosophila brain mediate the response of lifespan to nutrition. Aging Cell. 2010;9:336-46 pubmed publisher..of an interaction between these mNSCs, nutrition and sleep, further emphasising the functional homology between the DILP-producing neurosecretory cells in the Drosophila brain and the hypothalamus of mammals in their roles as ..
- 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
- Arquier N, Geminard C, Bourouis M, Jarretou G, Honegger B, Paix A, et al. Drosophila ALS regulates growth and metabolism through functional interaction with insulin-like peptides. Cell Metab. 2008;7:333-8 pubmed publisher..In Drosophila, a family of seven insulin-like peptides, called Dilps, activate a common insulin receptor. Some Dilp peptides carry both metabolic and growth functions, raising the possibility that various binding partners specify ..
- 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. We discuss physiological differences between mammals and insects that may explain the unexpected survival of lean, 'diabetic' flies. ..
- Wang M, Bohmann D, Jasper H. JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling. Cell. 2005;121:115-25 pubmed..The convergence of JNK signaling and IIS on Foxo provides a model to explain the effects of stress and nutrition on longevity. ..
- Kréneisz O, Chen X, Fridell Y, Mulkey D. Glucose increases activity and Ca2+ in insulin-producing cells of adult Drosophila. Neuroreport. 2010;21:1116-20 pubmed publisher..These results provide the first detailed characterization of electrical properties of IPCs of adult Drosophila and suggest that these cells sense glucose by a mechanism similar to mammalian pancreatic ? cells. ..
- 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..Loss of DILP2 increased lifespan and loss of DILP6 reduced growth, while loss of DILP7 did not affect fertility, contrary to its ..
- Enell L, Kapan N, Söderberg J, Kahsai L, Nassel D. Insulin signaling, lifespan and stress resistance are modulated by metabotropic GABA receptors on insulin producing cells in the brain of Drosophila. PLoS ONE. 2010;5:e15780 pubmed publisher..A set of insulin producing cells (IPCs) in the Drosophila brain that express three ILPs (DILP2, 3 and 5) have been the main focus of interest in hormonal DILP signaling...
- Xu K, Zheng X, Sehgal A. Regulation of feeding and metabolism by neuronal and peripheral clocks in Drosophila. Cell Metab. 2008;8:289-300 pubmed publisher..We propose that the input of neuronal clocks and clocks in metabolic tissues is coordinated to provide effective energy homeostasis...
- Wessells R, Fitzgerald E, Piazza N, Ocorr K, Morley S, Davies C, et al. d4eBP acts downstream of both dTOR and dFoxo to modulate cardiac functional aging in Drosophila. Aging Cell. 2009;8:542-52 pubmed publisher..cardiac aging nonautonomously through its activity in the insulin-producing cells, possibly by regulating dilp2 expression...
- Agrawal N, Padmanabhan N, Hasan G. Inositol 1,4,5- trisphosphate receptor function in Drosophila insulin producing cells. PLoS ONE. 2009;4:e6652 pubmed publisher..These data support a model where InsP(3)R activity in non-overlapping neuronal domains independently rescues larval itpr phenotypes by non-cell autonomous mechanisms. ..
- Wang S, Tulina N, Carlin D, Rulifson E. The origin of islet-like cells in Drosophila identifies parallels to the vertebrate endocrine axis. Proc Natl Acad Sci U S A. 2007;104:19873-8 pubmed..This ontogenic-molecular concordance suggests that a rudimentary brain endocrine axis was present in the common ancestor of humans and flies, where it orchestrated the islet-like endocrine functions of insulin and glucagon biology. ..
- Hull Thompson J, Muffat J, Sanchez D, Walker D, Benzer S, Ganfornina M, et al. Control of metabolic homeostasis by stress signaling is mediated by the lipocalin NLaz. PLoS Genet. 2009;5:e1000460 pubmed publisher..The JNK pathway and Lipocalins are structurally and functionally conserved, suggesting that similar interactions represent an evolutionarily conserved system for the control of metabolic homeostasis. ..
- 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..of IIS, by ablation of Drosophila insulin-like peptide (DILP)-producing median neurosecretory cells, knockout of dilp2, dilp3 or dilp5 genes, expression of a dominant-negative DILP-receptor (InR) transgene or knockout of Lnk, results ..
- Erion R, DiAngelo J, Crocker A, Sehgal A. Interaction between sleep and metabolism in Drosophila with altered octopamine signaling. J Biol Chem. 2012;287:32406-14 pubmed
- Jansen A, Nassel D, Madsen K, Jung A, Gether U, Kjaerulff O. PICK1 expression in the Drosophila central nervous system primarily occurs in the neuroendocrine system. J Comp Neurol. 2009;517:313-32 pubmed publisher..The PICK1-positive cells include neurosecretory cells that produce the insulin-like peptide dILP2. PICK1 expression in insulin-producing cells also occurs in mammals, as it was also observed in a rat insulinoma ..
- 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. ..
- Rulifson E, Kim S, Nusse R. Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science. 2002;296:1118-20 pubmed..Interestingly, the phenotype of flies lacking IPCs includes certain features of diabetes mellitus. ..
- Stafford J, Lynd K, Jung A, Gordon M. Integration of taste and calorie sensing in Drosophila. J Neurosci. 2012;32:14767-74 pubmed publisher..Our results are consistent with the existence of a taste-independent calorie sensor in flies, and suggest that calorie-based reward modifies long-term feeding preferences. ..
- Delanoue R, Slaidina M, Leopold P. The steroid hormone ecdysone controls systemic growth by repressing dMyc function in Drosophila fat cells. Dev Cell. 2010;18:1012-21 pubmed publisher..In conclusion, the present work reveals an unexpected function of dMyc in the systemic control of growth in response to steroid hormone signaling. ..
- Mattaliano M, Montana E, Parisky K, Littleton J, Griffith L. The Drosophila ARC homolog regulates behavioral responses to starvation. Mol Cell Neurosci. 2007;36:211-21 pubmed..This suggests that there are multiple modes of communication between the pars and the ring gland that control starvation-induced behavioral responses. ..
- Bauer J, Chang C, Morris S, Hozier S, Andersen S, Waitzman J, et al. Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling. Proc Natl Acad Sci U S A. 2007;104:13355-60 pubmed..DN-Dmp53-dependent lifespan extension is accompanied by reduction of Drosophila insulin-like peptide 2 (dILP2) mRNA levels and reduced insulin signaling (IIS) in the fat body, which suggests that Dmp53 may affect lifespan by ..
- Ballard S, Jarolimova J, Wharton K. Gbb/BMP signaling is required to maintain energy homeostasis in Drosophila. Dev Biol. 2010;337:375-85 pubmed publisher..Overall, our results implicate Gbb/BMP signaling as a new pathway critical for positive regulation of nutrient storage and energy homeostasis during development. ..
- Hewes R, Gu T, Brewster J, Qu C, Zhao T. Regulation of secretory protein expression in mature cells by DIMM, a basic helix-loop-helix neuroendocrine differentiation factor. J Neurosci. 2006;26:7860-9 pubmed
- Tsuda M, Kobayashi T, Matsuo T, Aigaki T. Insulin-degrading enzyme antagonizes insulin-dependent tissue growth and Abeta-induced neurotoxicity in Drosophila. FEBS Lett. 2010;584:2916-20 pubmed publisher..Using dIde(KO) as a model, further investigations into the biological functions of IDE and its role in the pathogenesis of DM2 and AD can be made...
- Marshall L, Rideout E, Grewal S. Nutrient/TOR-dependent regulation of RNA polymerase III controls tissue and organismal growth in Drosophila. EMBO J. 2012;31:1916-30 pubmed publisher..Thus, stimulation of Pol III is a key downstream effector of TOR in the control of cellular and systemic growth. ..
- 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...
- 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. ..
- 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..Our findings demonstrate that Mnb/Dyrk1a regulates food intake through the evolutionary conserved Sir2-FOXO-sNPF/NPY pathway in Drosophila melanogaster and mammals...
- Crocker A, Shahidullah M, Levitan I, Sehgal A. Identification of a neural circuit that underlies the effects of octopamine on sleep:wake behavior. Neuron. 2010;65:670-81 pubmed publisher..These studies define the cellular and molecular basis of octopamine action and suggest that the PI is a sleep:wake-regulating neuroendocrine structure like the mammalian hypothalamus. ..
- Luo J, Liu Y, Nassel D. Insulin/IGF-regulated size scaling of neuroendocrine cells expressing the bHLH transcription factor Dimmed in Drosophila. PLoS Genet. 2013;9:e1004052 pubmed publisher..We suggest that the dInR-mediated scaling of neuroendocrine cells is part of a plasticity that adapts the secretory capacity to changing physiological conditions and nutrient-dependent organismal growth. ..
- 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..and redundancy between DILPs, we used RNA interference to lower specifically the transcript and protein levels of dilp2, the most highly expressed of the mNSC-derived DILPs...
- Colombani J, Raisin S, Pantalacci S, Radimerski T, Montagne J, Leopold P. A nutrient sensor mechanism controls Drosophila growth. Cell. 2003;114:739-49 pubmed..Our results demonstrate that the fat body functions as a nutrient sensor that restricts global growth through a humoral mechanism. ..
- 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..We expect that this study will promote investigation of such possible direct signal sensing mechanisms by mammalian myeloid progenitors...
- Geminard C, Rulifson E, Leopold P. Remote control of insulin secretion by fat cells in Drosophila. Cell Metab. 2009;10:199-207 pubmed publisher..liver and white fat, couples the level of circulating Dilps with dietary amino acid levels by remotely controlling Dilp release through a TOR/RAPTOR-dependent mechanism...
- LaFever L, Drummond Barbosa D. Direct control of germline stem cell division and cyst growth by neural insulin in Drosophila. Science. 2005;309:1071-3 pubmed..We also reveal a crucial direct role of DILPs in controlling germline cyst growth and vitellogenesis. ..
- 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..Of these, reduced dilp2 expressed in the brain has been associated with longevity assurance when over-expression of dfoxo in fat bodies ..
- 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. ..
- 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..These results identify a molecular mechanism that underlies the crosstalk between these two hormones and add a new layer of complexity to the well-characterized role of bantam in growth control. ..
- 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 ..
- 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.