medigraphic.com
ISSN 2395-8723 (Electronic)
ISSN 1405-888X (Print)
TIP Revista Especializada en Ciencias Químico-Biológicas

2016, Number 2

<< Back Next >>

TIP Rev Esp Cienc Quim Biol 2016; 19 (2)

Growth and Metabolism: Regulation and the Insulin Pathway from a Fruit Fly’s Viewpoint

Otero-Moreno D, Peña-Rangel MT, Riesgo-Escovar JR

Language: Spanish
References: 77
Page: 116-126
PDF size: 752.98 Kb.


ABSTRACT

The fruit fly Drosophila melanogaster is a model genetic organism that has recently been used with great success in the study of metabolism and growth controls. In spite of several differences with vertebrates, commonalities are many and extensive. In flies, the insulin pathway, homologous to the vertebrate pathway, regulates metabolism, growth, and proliferation through a single, common membrane receptor. This pathway, jointly taking over the functions exerted by vertebrate insulin and insulin-like peptides, is regulated by nutrient levels (dietary carbohydrates and proteins), and by hormonal control (juvenile hormone, ecdysone, upd2, adipokinetic hormone, Ilp8). This means that normally growth, size, and harmony of body parts are adapted to the nutritional status, influencing life expectancy and reproduction, and resulting in the wild type in reaching typical adult sizes and proportions, as expected from the bauplan. Mutations and deviations normally end up in disproportionate growth of body parts, overall reduced size and reproduction, and, ultimately, death.


REFERENCES

  1. Owusu-Ansah, E. & Perrimon, N. Modeling metabolic homeostasis and nutrient sensing in Drosophila: implications for aging and metabolic diseases. Dis. Model Mech. 7, 343-350, doi:10.1242/dmm.012989 (2014).

  2. Smith, W. W., Thomas, J., Liu, J., Li, T. & Moran, T. H. From fat fruit fly to human obesity. Physiol. Behav. 136, 15-21, doi:10.1016/j.physbeh.2014.01.017 (2014).

  3. Rubin, G. M. Drosophila melanogaster as an experimental organism. Science 240, 1453-1459 (1988).

  4. Teleman, A. A. Molecular mechanisms of metabolic regulation by insulin in Drosophila. Biochem. J. 425, 13-26, doi:10.1042/ BJ20091181 (2010).

  5. Rajan, A. & Perrimon, N. Drosophila cytokine unpaired 2 regulates physiological homeostasis by remotely controlling insulin secretion. Cell 151, 123-137, doi:10.1016/j.cell.2012.08.019 (2012).

  6. Vallejo, C. G., Juárez-Carreño, S., Bolívar, J., Morante, J. & Domínguez, M. A brain circuit that synchronizes growth and maduration revealed through Dilp8 binding to Lgr3. Science 350, doi:10.1126/science.aac676 (2015).

  7. Colombani, J. et al. Drosophila Lgr3 Couples Organ Growth with Maturation and Ensures Developmental Stability. Curr. Biol. 25, 2723-2729, doi:10.1016/j.cub.2015.09.020 (2015).

  8. Colombani, J., Andersen, D. S. & Leopold, P. Secreted peptide Dilp8 coordinates Drosophila tissue growth with developmental timing. Science 336, 582-585, doi:10.1126/science.1216689 (2012).

  9. Garelli, A., Gontijo, A. M., Miguela, V., Caparros, E. & Domínguez, M. Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation. Science 336, 579-582, doi:10.1126/science.1216735 (2012).

  10. Pool, A. H. & Scott, K. Feeding regulation in Drosophila. Curr. Opin. Neurobiol. 29, 57-63, doi:10.1016/j.conb.2014.05.008 (2014).

  11. Kim, J. & Neufeld, T. P. Dietary sugar promotes systemic TOR activation in Drosophila through AKH-dependent selective secretion of Dilp3. Nat. Commun. 6, 6846, doi:10.1038/ncomms7846 (2015).

  12. Koyama, T., Mendes, C. C. & Mirth, C. K. Mechanisms regulating nutrition-dependent developmental plasticity through organspecific effects in insects. Front Physiol. 4, 263, doi:10.3389/fphys.2013.00263 (2013).

  13. Kamakura, M. Royalactin induces queen differentiation in honeybees. Nature 473, 478-483, doi:10.1038/nature10093 (2011).

  14. Andersen, D. S., Colombani, J. & Leopold, P. Drosophila growth and development: keeping things in proportion. Cell Cycle 11, 2971-2972, doi:10.4161/cc.21466 (2012).

  15. Sheldon, A. L., Zhang, J., Fei, H. & Levitan, I. B. SLOB, a SLOWPOKE channel binding protein, regulates insulin pathway signaling and metabolism in Drosophila. PLoS One 6, e23343, doi:10.1371/journal.pone.0023343 (2011).

  16. Fridell, Y. W. et al. Increased uncoupling protein (UCP) activity in Drosophila insulin-producing neurons attenuates insulin signaling and extends lifespan. Aging (Albany NY) 1, 699-713 (2009).

  17. Kreneisz, O., Chen, X., Fridell, Y. W. & Mulkey, D. K. Glucose increases activity and Ca2+ in insulin-producing cells of adult Drosophila. Neuroreport 21, 1116-1120, doi:10.1097/ WNR.0b013e3283409200 (2010).

  18. Nassel, D. R., Kubrak, O. I., Liu, Y., Luo, J. & Lushchak, O. V. Factors that regulate insulin producing cells and their output in Drosophila. Front Physiol. 4, 252, doi:10.3389/fphys.2013.00252 (2013).

  19. The FlyBase database of the Drosophila genome projects and community literature. Nucleic Acids Res. 31, 172-175 (2003).

  20. Colombani, J. et al. A nutrient sensor mechanism controls Drosophila growth. Cell 114, 739-749 (2003).

  21. Kwak, S. J. et al. Drosophila adiponectin receptor in insulin producing cells regulates glucose and lipid metabolism by controlling insulin secretion. PLoS One 8, e68641, doi:10.1371/journal.pone.0068641 (2013).

  22. Pool, A. H. et al. Four GABAergic interneurons impose feeding restraint in Drosophila. Neuron 83, 164-177, doi:10.1016/j. neuron.2014.05.006 (2014).

  23. Okamoto, H. & Nishimura, E. K. Signaling from Glia and Cholinergic Neurons Controls Nutrient-Dependent Production of an Insulin-like Peptide for Drosophila Body Growth. Dev. Cell 35, 295-310 (2015).

  24. Rulifson, E. J., Kim, S. K. & Nusse, R. Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science 296, 1118-1120, doi:10.1126/science.1070058 (2002).

  25. R, N. D. & J, V. B. Insulin/IGF signaling in Drosophila and other insects: factors that regulate production, release and postrelease action of the insulin-like peptides. Cell. Mol. Life Sci., doi:10.1007/s00018-015-2063-3 (2015).

  26. Palu, R. A. S. & Thummel, C. S. Linking Nutrients to Growth through a Positive Feedback Loop. Dev. Cell 35, 265-266, doi:http://dx.doi.org/10.1016/j.devcel.2015.10.026 (2015).

  27. Brogiolo, W. et al. An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Curr. Biol. 11, 213-221 (2001).

  28. Broughton, S. J. et al. Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proceedings of the National Academy of Sciences of the United States of America 102, 3105-3110, doi:10.1073/pnas.0405775102 (2005).

  29. Alic, N., Hoddinott, M. P., Vinti, G. & Partridge, L. Lifespan extension by increased expression of the Drosophila homologue of the IGFBP7 tumour suppressor. Aging Cell 10, 137-147, doi:10.1111/j.1474-9726.2010.00653.x (2011).

  30. Arquier, N. et al. Drosophila ALS regulates growth and metabolism through functional interaction with insulin-like peptides. Cell Metab. 7, 333-338, doi:10.1016/j.cmet.2008.02.003 (2008).

  31. Okamoto, N. et al. A secreted decoy of InR antagonizes insulin/IGF signaling to restrict body growth in Drosophila. Genes Dev. 27, 87-97, doi:10.1101/gad.204479.112 (2013).

  32. Lee, K. S. et al. Drosophila short neuropeptide F signalling regulates growth by ERK-mediated insulin signalling. Nat. Cell Biol. 10, 468-475, doi:10.1038/ncb1710 (2008).

  33. Kapan, N., Lushchak, O. V., Luo, J. & Nassel, D. R. Identified peptidergic neurons in the Drosophila brain regulate insulin-producing cells, stress responses and metabolism by coexpressed short neuropeptide F and corazonin. Cell Mol. Life Sci. 69, 4051-4066, doi:10.1007/s00018-012-1097-z (2012).

  34. Kaplan, D. D., Zimmermann, G., Suyama, K., Meyer, T. & Scott, M. P. A nucleostemin family GTPase, NS3, acts in serotonergic neurons to regulate insulin signaling and control body size. Genes Dev. 22, 1877-1893, doi:10.1101/gad.1670508 (2008).

  35. Luo, J., Becnel, J., Nichols, C. D. & Nassel, D. R. Insulin-producing cells in the brain of adult Drosophila are regulated by the serotonin 5-HT1A receptor. Cell Mol. Life Sci. 69, 471-484, doi:10.1007/s00018-011-0789-0 (2012).

  36. Birse, R. T., Soderberg, J. A., Luo, J., Winther, A. M. & Nassel, D. R. Regulation of insulin-producing cells in the adult Drosophila brain via the tachykinin peptide receptor DTKR. The Journal of experimental biology 214, 4201-4208, doi:10.1242/jeb.062091 (2011).

  37. Miyamoto, T., Wright, G. & Amrein, H. Nutrient sensors. Curr. Biol. 23, R369-373, doi:10.1016/j.cub.2013.04.002 (2013).

  38. Miyamoto, T. & Amrein, H. Diverse roles for the Drosophila fructose sensor Gr43a. Fly (Austin) 8, 19-25, doi:10.4161/ fly.27241 (2014).

  39. Nassel, D. R. & Broeck, J. V. Insulin/IGF signaling in Drosophila and other insects: factors that regulate production, release and post-release action of the insulin-like peptides. Cell Mol. Life Sci., doi:10.1007/s00018-015-2063-3 (2015).

  40. Lushchak, O. V., Carlsson, M. A. & Nassel, D. R. Food odors trigger an endocrine response that affects food ingestion and metabolism. Cell Mol. Life Sci. 72, 3143-3155, doi:10.1007/s00018-015-1884-4 (2015).

  41. Fernández, 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. 14, 3373-3384 (1995).

  42. Bohni, R. et al. Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell 97, 865-875 (1999).

  43. Slack, C. et al. Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk. PLoS Genet. 6, e1000881, doi:10.1371/journal.pgen.1000881 (2010).

  44. 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. 5, e1000596, doi:10.1371/journal.pgen.1000596 (2009).

  45. Almudi, I., Poernbacher, I., Hafen, E. & Stocker, H. The Lnk/ SH2B adaptor provides a fail-safe mechanism to establish the Insulin receptor-Chico interaction. Cell Commun. Signal 11, 26, doi:10.1186/1478-811X-11-26 (2013).

  46. Leevers, S. J., Weinkove, D., MacDougall, L. K., Hafen, E. & Waterfield, M. D. The Drosophila phosphoinositide 3-kinase Dp110 promotes cell growth. Embo. J. 15, 6584-6594 (1996).

  47. Alessi, D. R. et al. 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase. Curr. Biol. 7, 776-789 (1997).

  48. Verdu, J., Buratovich, M. A., Wilder, E. L. & Birnbaum, M. J. Cellautonomous regulation of cell and organ growth in Drosophila by Akt/PKB. Nat. Cell Biol. 1, 500-506, doi:10.1038/70293 (1999).

  49. Huang, H. et al. PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development. Development 126, 5365-5372 (1999).

  50. Papadopoulou, D., Bianchi, M. W. & Bourouis, M. Functional studies of shaggy/glycogen synthase kinase 3 phosphorylation sites in Drosophila melanogaster melanogaster. Mol. Cell Biol. 24, 4909-4919, doi:10.1128/MCB.24.11.4909-4919.2004 (2004).

  51. Junger, M. A. et al. The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J Biol 2, 20, doi:10.1186/1475- 4924-2-20 (2003).

  52. Kramer, J. M., Slade, J. D. & Staveley, B. E. foxo is required for resistance to amino acid starvation in Drosophila. Genome 51, 668-672, doi:10.1139/G08-047 (2008).

  53. Kramer, J. M., Davidge, J. T., Lockyer, J. M. & Staveley, B. E. Expression of Drosophila FOXO regulates growth and can phenocopy starvation. BMC Dev. Biol. 3, 5, doi:10.1186/1471-213X-3-5 (2003).

  54. Potter, C. J., Huang, H. & Xu, T. Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 105, 357-368 (2001).

  55. Tapon, N., Ito, N., Dickson, B. J., Treisman, J. E. & Hariharan, I. K. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell 105, 345-355 (2001).

  56. Ito, N. & Rubin, G. M. gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle. Cell 96, 529-539 (1999).

  57. Zhang, Y. et al. Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat. Cell Biol. 5, 578-581, doi:10.1038/ncb999 (2003).

  58. Saucedo, L. J. et al. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat. Cell Biol. 5, 566- 571, doi:10.1038/ncb996 (2003).

  59. Potter, C. J., Pedraza, L. G. & Xu, T. Akt regulates growth by directly phosphorylating Tsc2. Nat. Cell Biol. 4, 658-665, doi:10.1038/ncb840 (2002).

  60. Wang, B. et al. A hormone-dependent module regulating energy balance. Cell 145, 596-606, doi:10.1016/j.cell.2011.04.013 (2011).

  61. Oldham, S. & Hafen, E. Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol. 13, 79-85 (2003).

  62. Seto, B. Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer. Clin. Transl. Med. 1, 29, doi:10.1186/2001-1326-1-29 (2012).

  63. Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P. & Guan, K. L. Regulation of TORC1 by Rag GTPases in nutrient response. Nat. Cell Biol. 10, 935-945, doi:10.1038/ncb1753 (2008).

  64. Chantranupong, L., Wolfson, R. L. & Sabatini, D. M. Nutrientsensing mechanisms across evolution. Cell 161, 67-83, doi:10.1016/j.cell.2015.02.041 (2015).

  65. Li, L. et al. Regulation of mTORC1 by the Rab and Arf GTPases. J. Biol. Chem. 285, 19705-19709, doi:10.1074/jbc.C110.102483 (2010).

  66. Miron, M., Lasko, P. & Sonenberg, N. Signaling from Akt to FRAP/TOR targets both 4E-BP and S6K in Drosophila melanogaster. Mol. Cell Biol. 23, 9117-9126 (2003).

  67. Stewart, M. J., Berry, C. O., Zilberman, F., Thomas, G. & Kozma, S. C. The Drosophila p70s6k homolog exhibits conserved regulatory elements and rapamycin sensitivity. Proceedings of the National Academy of Sciences of the United States of America 93, 10791-10796 (1996).

  68. Montagne, J. et al. Drosophila S6 kinase: a regulator of cell size. Science 285, 2126-2129 (1999).

  69. Hernández, G. & Sierra, J. M. Translation initiation factor eIF-4E from Drosophila: cDNA sequence and expression of the gene. Biochimica et biophysica acta 1261, 427-431 (1995).

  70. Hardie, D. G. & Pan, D. A. Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase. Biochem. Soc. Trans. 30, 1064-1070, doi:10.1042/ (2002).

  71. Pan, D. A. & Hardie, D. G. A homologue of AMP-activated protein kinase in Drosophila melanogaster is sensitive to AMP and is activated by ATP depletion. Biochem. J. 367, 179-186, doi:10.1042/BJ20020703 (2002).

  72. Haselton, A. T. & Fridell, Y. W. Adult Drosophila melanogaster as a model for the study of glucose homeostasis. Aging (Albany NY) 2, 523-526 (2010).

  73. Baker, K. D. & Thummel, C. S. Diabetic larvae and obese fliesemerging studies of metabolism in Drosophila. Cell Metab. 6, 257-266, doi:10.1016/j.cmet.2007.09.002 (2007).

  74. Murillo-Maldonado, J. M., Sánchez-Chávez, G., Salgado, L. M., Salceda, R. & Riesgo-Escovar, J. R. Drosophila insulin pathway mutants affect visual physiology and brain function besides growth, lipid, and carbohydrate metabolism. Diabetes 60, 1632-1636, doi:10.2337/db10-1288 (2011).

  75. Murillo-Maldonado, J. M., Zeineddine, F. B., Stock, R., Thackeray, J. & Riesgo-Escovar, J. R. Insulin receptor-mediated signaling via phospholipase C-gamma regulates growth and differentiation in Drosophila. PLoS One 6, e28067, doi:10.1371/journal. pone.0028067 (2011).

  76. Haselton, A. et al. Partial ablation of adult Drosophila insulinproducing neurons modulates glucose homeostasis and extends life span without insulin resistance. Cell Cycle 9, 3063-3071, doi:10.4161/cc.9.15.12458 (2010).

  77. Casanueva, E., Kaufer-Horwitz, M., Pérez-Lizaur, A. B. & Arroyo, P. Nutriología Médica. (Editorial Médica Panamericana, 2008).




2020     |     www.medigraphic.com