Endocrine

, 40:1

Apelin, diabetes, and obesity

  • Isabelle Castan-Laurell
  • Cédric Dray
  • Camille Attané
  • Thibaut Duparc
  • Claude Knauf
  • Philippe Valet
Review

Abstract

Apelin is a peptide known as the ligand of the G-protein-coupled receptor APJ. Several active apelin forms exist such as apelin-36, apelin-17, apelin-13, and the pyroglutamated form of apelin-13. Apelin and APJ are expressed in the central nervous system, particularly in the hypothalamus and in many peripheral tissues. Apelin has been shown to be involved in the regulation of cardiovascular and fluid homeostasis, food intake, cell proliferation, and angiogenesis. In addition to be an ubiquitous peptide, apelin is also produced and secreted by adipocytes and thus considered as an adipokine. This has opened a new field of investigation establishing a link between apelin and metabolic disorders (obesity, type 2 diabetes, etc.) which is the focus of the present review. Several studies, but not all, have reported an increase of plasma apelin concentrations in humans and in animal models with different metabolic pathologies. Moreover, important roles for apelin both in glucose and lipid metabolism have been highlighted as well as the associated signaling pathways. Apelin appears as a beneficial adipokine with anti-obesity and anti-diabetic properties and thus as a promising therapeutic target in metabolic disorders.

Keywords

Apelin Insulin resistance Obesity Glucose metabolism Lipid metabolism 

References

  1. 1.
    B.F. O’Dowd, M. Heiber, A. Chan, H.H. Heng, L.C. Tsui, J.L. Kennedy, X. Shi, A. Petronis, S.R. George, T. Nguyen, Gene 136, 355 (1993)PubMedCrossRefGoogle Scholar
  2. 2.
    A.D. Medhurst, C.A. Jennings, M.J. Robbins, R.P. Davis, C. Ellis, K.Y. Winborn, K.W. Lawrie, G. Hervieu, G. Riley, J.E. Bolaky, N.C. Herrity, P. Murdock, J.G. Darker, J. Neurochem. 84, 1162 (2003)PubMedCrossRefGoogle Scholar
  3. 3.
    E. Devic, K. Rizzoti, S. Bodin, B. Knibiehler, Y. Audigier, Mech. Dev. 84, 199 (1999)PubMedCrossRefGoogle Scholar
  4. 4.
    S. El Messari, X. Iturrioz, C. Fassot, N. De Mota, D. Roesch, C. Llorens-Cortes, J. Neurochem. 90, 1290 (2004)PubMedCrossRefGoogle Scholar
  5. 5.
    M.J. Moon, D.Y. Oh, J.S. Moon, D.K. Kim, J.I. Hwang, J.Y. Lee, J.I. Kim, S. Cho, H.B. Kwon, J.Y. Seong, Mol. Cell. Endocrinol. 277, 51 (2007)PubMedCrossRefGoogle Scholar
  6. 6.
    B. Masri, H. Lahlou, H. Mazarguil, B. Knibiehler, Y. Audigier, Biochem. Biophys. Res. Commun. 290, 539 (2002)PubMedCrossRefGoogle Scholar
  7. 7.
    B. Masri, N. Morin, M. Cornu, B. Knibiehler, Y. Audigier, FASEB J. 18, 1909 (2004)PubMedGoogle Scholar
  8. 8.
    K. Tatemoto, M. Hosoya, Y. Habata, R. Fujii, T. Kakegawa, M.X. Zou, Y. Kawamata, S. Fukusumi, S. Hinuma, C. Kitada, T. Kurokawa, H. Onda, M. Fujino, Biochem. Biophys. Res. Commun. 251, 471 (1998)PubMedCrossRefGoogle Scholar
  9. 9.
    D.K. Lee, R. Cheng, T. Nguyen, T. Fan, A.P. Kariyawasam, Y. Liu, D.H. Osmond, S.R. George, B.F. O’Dowd, J. Neurochem. 74, 34 (2000)PubMedCrossRefGoogle Scholar
  10. 10.
    M.J. Kleinz, A.P. Davenport, Pharmacol. Ther. 107, 198 (2005)PubMedCrossRefGoogle Scholar
  11. 11.
    C. Carpene, C. Dray, C. Attane, P. Valet, M.P. Portillo, I. Churruca, F.I. Milagro, I. Castan-Laurell, J. Physiol. Biochem. 63, 359 (2007)PubMedCrossRefGoogle Scholar
  12. 12.
    G. Foldes, F. Horkay, I. Szokodi, O. Vuolteenaho, M. Ilves, K.A. Lindstedt, M. Mayranpaa, B. Sarman, L. Seres, R. Skoumal, Z. Lako-Futo, R. deChatel, H. Ruskoaho, M. Toth, Biochem. Biophys. Res. Commun. 308, 480 (2003)PubMedCrossRefGoogle Scholar
  13. 13.
    D.K. Lee, V.R. Saldivia, T. Nguyen, R. Cheng, S.R. George, B.F. O’Dowd, Endocrinology 146, 231 (2005)PubMedCrossRefGoogle Scholar
  14. 14.
    Y. Kawamata, Y. Habata, S. Fukusumi, M. Hosoya, R. Fujii, S. Hinuma, N. Nishizawa, C. Kitada, H. Onda, O. Nishimura, M. Fujino, Biochim. Biophys. Acta 1538, 162 (2001)PubMedCrossRefGoogle Scholar
  15. 15.
    N. De Mota, A. Reaux-Le Goazigo, S. El Messari, N. Chartrel, D. Roesch, C. Dujardin, C. Kordon, H. Vaudry, F. Moos, C. Llorens-Cortes, Proc. Natl. Acad. Sci. USA 101, 10464 (2004)PubMedCrossRefGoogle Scholar
  16. 16.
    J.J. Maguire, M.J. Kleinz, S.L. Pitkin, A.P. Davenport, Hypertension 54, 598 (2009)PubMedCrossRefGoogle Scholar
  17. 17.
    X. Fan, N. Zhou, X. Zhang, M. Mukhtar, Z. Lu, J. Fang, G.C. DuBois, R.J. Pomerantz, Biochemistry 42, 10163 (2003)PubMedCrossRefGoogle Scholar
  18. 18.
    M. Hosoya, Y. Kawamata, S. Fukusumi, R. Fujii, Y. Habata, S. Hinuma, C. Kitada, S. Honda, T. Kurokawa, H. Onda, O. Nishimura, M. Fujino, J. Biol. Chem. 275, 21061 (2000)PubMedCrossRefGoogle Scholar
  19. 19.
    D. Calebiro, V.O. Nikolaev, L. Persani, M.J. Lohse, Trends Pharmacol. Sci. 31, 221 (2010)PubMedCrossRefGoogle Scholar
  20. 20.
    D.K. Lee, S.S. Ferguson, S.R. George, B.F. O’Dowd, Biochem. Biophys. Res. Commun. 395, 185 (2010)PubMedCrossRefGoogle Scholar
  21. 21.
    N.J. Macaluso, S.L. Pitkin, J.J. Maguire, A.P. Davenport, R.C. Glen, ChemMedChem 6, 1017 (2011)PubMedCrossRefGoogle Scholar
  22. 22.
    X. Iturrioz, R. Alvear-Perez, N. De Mota, C. Franchet, F. Guillier, V. Leroux, H. Dabire, M. Le Jouan, H. Chabane, R. Gerbier, D. Bonnet, A. Berdeaux, B. Maigret, J.L. Galzi, M. Hibert, C. Llorens-Cortes, FASEB J. 24, 1506 (2010)PubMedCrossRefGoogle Scholar
  23. 23.
    C. Mesmin, M. Dubois, F. Becher, F. Fenaille, E. Ezan, Rapid Commun. Mass Spectrom. 24, 2875 (2010)PubMedCrossRefGoogle Scholar
  24. 24.
    C. Vickers, P. Hales, V. Kaushik, L. Dick, J. Gavin, J. Tang, K. Godbout, T. Parsons, E. Baronas, F. Hsieh, S. Acton, M. Patane, A. Nichols, P. Tummino, J. Biol. Chem. 277, 14838 (2002)PubMedCrossRefGoogle Scholar
  25. 25.
    A.Z. Kalea, D. Batlle, Curr. Opin. Investig. Drugs 11, 273 (2010)PubMedGoogle Scholar
  26. 26.
    K. Kuba, Y. Imai, T. Ohto-Nakanishi, J.M. Penninger, Pharmacol. Ther. 128, 119 (2010)PubMedCrossRefGoogle Scholar
  27. 27.
    S.M. Bindom, C.P. Hans, H. Xia, A.H. Boulares, E. Lazartigues, Diabetes 59, 2540 (2010)PubMedCrossRefGoogle Scholar
  28. 28.
    K. Tatemoto, Nippon Rinsho 58, 737 (2000)PubMedGoogle Scholar
  29. 29.
    J. Boucher, B. Masri, D. Daviaud, S. Gesta, C. Guigne, A. Mazzucotelli, I. Castan-Laurell, I. Tack, B. Knibiehler, C. Carpene, Y. Audigier, J.S. Saulnier-Blache, P. Valet, Endocrinology 146, 1764 (2005)PubMedCrossRefGoogle Scholar
  30. 30.
    D. Daviaud, J. Boucher, S. Gesta, C. Dray, C. Guigne, D. Quilliot, A. Ayav, O. Ziegler, C. Carpene, J.S. Saulnier-Blache, P. Valet, I. Castan-Laurell, FASEB J 20, 1528 (2006)PubMedCrossRefGoogle Scholar
  31. 31.
    S. Han, G. Wang, X. Qi, E.W. Englander, G.H. Greeley Jr., Am. J. Physiol. Gastrointest. Liver Physiol. 295, G1068 (2008)PubMedCrossRefGoogle Scholar
  32. 32.
    N.J. Leeper, M.M. Tedesco, Y. Kojima, G.M. Schultz, R.K. Kundu, E.A. Ashley, P.S. Tsao, R.L. Dalman, T. Quertermous, Am. J. Physiol. Heart Circ. Physiol. 296, 1329 (2009)CrossRefGoogle Scholar
  33. 33.
    A. Mazzucotelli, C. Ribet, I. Castan-Laurell, D. Daviaud, C. Guigne, D. Langin, P. Valet, Regul. Pept. 150, 33 (2008)PubMedCrossRefGoogle Scholar
  34. 34.
    S. Lorente-Cebrian, M. Bustos, A. Marti, J.A. Martinez, M.J. Moreno-Aliaga, Mol. Nutr. Food Res. 54(Suppl 1), S104 (2010)PubMedCrossRefGoogle Scholar
  35. 35.
    N. Perez-Echarri, P. Perez-Matute, B. Marcos-Gomez, J.A. Martinez, M.J. Moreno-Aliaga, Br. J. Nutr. 101, 1059 (2009)PubMedCrossRefGoogle Scholar
  36. 36.
    L. Martin de Santa Olalla, F.J. Sánchez Muniz, M.P. Vaquero, Nutr. Hosp. 24, 113 (2009)PubMedGoogle Scholar
  37. 37.
    W.W. Hung, T.J. Hsieh, T. Lin, P.C. Chou, P.J. Hsiao, K.D. Lin, S.J. Shin, Cardiovasc. Drugs Ther. 25, 3 (2011)PubMedCrossRefGoogle Scholar
  38. 38.
    C. Foussal, O. Lairez, D. Calise, A. Pathak, C. Guilbeau-Frugier, P. Valet, A. Parini, O. Kunduzova, FEBS Lett. 584, 2363 (2010)PubMedCrossRefGoogle Scholar
  39. 39.
    X.J. Zeng, S.P. Yu, L. Zhang, L. Wei, Exp. Cell Res. 316, 1773 (2010)PubMedCrossRefGoogle Scholar
  40. 40.
    Q. He, Z. Gao, J. Yin, J. Zhang, Z. Yun, J. Ye, Am. J. Physiol. Endocrinol. Metab. 300, E877 (2011)PubMedCrossRefGoogle Scholar
  41. 41.
    K. Geiger, A. Muendlein, N. Stark, C.H. Saely, M. Wabitsch, P. Fraunberger, H. Drexel, Horm. Metab. Res. 43, 380 (2011)PubMedCrossRefGoogle Scholar
  42. 42.
    A.J. Glassford, P. Yue, A.Y. Sheikh, H.J. Chun, S. Zarafshar, D.A. Chan, G.M. Reaven, T. Quertermous, P.S. Tsao, Am. J. Physiol. Endocrinol. Metab. 293, 1590 (2007)CrossRefGoogle Scholar
  43. 43.
    O. Kunduzova, N. Alet, N. Delesque-Touchard, L. Millet, I. Castan-Laurell, C. Muller, C. Dray, P. Schaeffer, J.P. Herault, P. Savi, F. Bono, P. Valet, FASEB J. 22, 4146 (2008)PubMedCrossRefGoogle Scholar
  44. 44.
    L. Wei, X. Hou, K. Tatemoto, Regul. Pept. 132, 27 (2005)PubMedCrossRefGoogle Scholar
  45. 45.
    I. Castan-Laurell, M. Vitkova, D. Daviaud, C. Dray, M. Kovacikova, Z. Kovacova, J. Hejnova, V. Stich, P. Valet, Eur. J. Endocrinol. 158, 905 (2008)PubMedCrossRefGoogle Scholar
  46. 46.
    B. Telejko, M. Kuzmicki, N. Wawrusiewicz-Kurylonek, J. Szamatowicz, A. Nikolajuk, A. Zonenberg, D. Zwierz-Gugala, W. Jelski, P. Laudanski, J. Wilczynski, A. Kretowski, M. Gorska, Diabetes Res. Clin. Pract. 87, 176 (2010)PubMedCrossRefGoogle Scholar
  47. 47.
    C. Dray, C. Debard, J. Jager, E. Disse, D. Daviaud, P. Martin, C. Attane, E. Wanecq, C. Guigne, F. Bost, J.F. Tanti, M. Laville, H. Vidal, P. Valet, I. Castan-Laurell, Am. J. Physiol. Endocrinol. Metab. 298, 1161 (2010)CrossRefGoogle Scholar
  48. 48.
    C. Attane, D. Daviaud, C. Dray, R. Dusaulcy, M. Masseboeuf, D. Prevot, C. Carpene, I. Castan-Laurell, P. Valet, J. Mol. Endocrinol. 46, 21 (2011)PubMedCrossRefGoogle Scholar
  49. 49.
    M.V. Heinonen, A.K. Purhonen, P. Miettinen, M. Paakkonen, E. Pirinen, E. Alhava, K. Akerman, K.H. Herzig, Regul. Pept. 130, 7 (2005)PubMedCrossRefGoogle Scholar
  50. 50.
    L. Li, G. Yang, Q. Li, Y. Tang, M. Yang, H. Yang, K. Li, Exp. Clin. Endocrinol. Diabetes 114, 544 (2006)PubMedCrossRefGoogle Scholar
  51. 51.
    F. Soriguer, L. Garrido-Sanchez, S. Garcia-Serrano, J.M. Garcia-Almeida, J. Garcia-Arnes, F.J. Tinahones, E. Garcia-Fuentes, Obes. Surg. 19, 1574 (2009)PubMedCrossRefGoogle Scholar
  52. 52.
    G. Erdem, T. Dogru, I. Tasci, A. Sonmez, S. Tapan, Exp. Clin. Endocrinol. Diabetes 116, 289 (2008)PubMedCrossRefGoogle Scholar
  53. 53.
    R. Zhang, C. Hu, C.R. Wang, X.J. Ma, Y.Q. Bao, J. Xu, J.Y. Lu, W. Qin, K.S. Xiang, W.P. Jia, Chin. Med. J. (Engl.) 122, 1273 (2009)Google Scholar
  54. 54.
    N.P. Kadoglou, H. Tsanikidis, A. Kapelouzou, I. Vrabas, I. Vitta, P.E. Karayannacos, C.D. Liapis, N. Sailer, Metabolism 59, 373 (2010)PubMedCrossRefGoogle Scholar
  55. 55.
    S. Aydin, Peptides 31, 2236 (2010)PubMedCrossRefGoogle Scholar
  56. 56.
    S. Tapan, E. Tascilar, A. Abaci, A. Sonmez, S. Kilic, M.K. Erbil, O. Ozcan, J. Pediatr. Endocrinol. Metab. 23, 1039 (2010)PubMedCrossRefGoogle Scholar
  57. 57.
    K. Ziora, J. Oswiecimska, E. Swietochowska, D. Ziora, Z. Ostrowska, M. Stojewska, E. Klimacka-Nawrot, A. Dyduch, B. Blonska-Fajfrowska, J. Clin. Endocrinol. Metab. 95, 2935 (2010)PubMedCrossRefGoogle Scholar
  58. 58.
    Reinehr, T., Woelfle, J., Roth, C.L.: Lack of association between apelin, insulin resistance, cardiovascular risk factors, and obesity in children: a longitudinal analysis. Metabolism. (2011). doi:10.1016/j.metabol.2011.02.005
  59. 59.
    C. Meral, E. Tascilar, F. Karademir, I.A. Tanju, F. Cekmez, O.M. Ipcioglu, C.N. Ercin, I. Gocmen, T. Dogru, J. Pediatr. Endocrinol. Metab. 23, 497 (2010)PubMedCrossRefGoogle Scholar
  60. 60.
    M.V. Heinonen, D.E. Laaksonen, T. Karhu, L. Karhunen, T. Laitinen, S. Kainulainen, A. Rissanen, L. Niskanen, K.H. Herzig, Nutr. Metab. Cardiovasc. Dis. 19, 626 (2009)PubMedCrossRefGoogle Scholar
  61. 61.
    C.N. Ercin, T. Dogru, S. Tapan, M. Kara, C. Haymana, N. Karadurmus, Y. Karslioglu, C. Acikel, Metabolism 59, 977 (2010)PubMedCrossRefGoogle Scholar
  62. 62.
    Y. Zhang, C. Shen, X. Li, G. Ren, X. Fan, F. Ren, N. Zhang, J. Sun, J. Yang, Chin. Med. J. 122, 1273 (2009)PubMedGoogle Scholar
  63. 63.
    M. Sorhede Winzell, C. Magnusson, B. Ahren, Regul. Pept. 131, 12 (2005)PubMedCrossRefGoogle Scholar
  64. 64.
    L. Guo, Q. Li, W. Wang, P. Yu, H. Pan, P. Li, Y. Sun, J. Zhang, Endocr. Res. 34, 142 (2009)PubMedCrossRefGoogle Scholar
  65. 65.
    C. Ringstrom, M.D. Nitert, H. Bennet, M. Fex, P. Valet, J.F. Rehfeld, L. Friis-Hansen, N. Wierup, Regul. Pept. 162, 44 (2010)PubMedCrossRefGoogle Scholar
  66. 66.
    C. Dray, C. Knauf, D. Daviaud, A. Waget, J. Boucher, M. Buleon, P.D. Cani, C. Attane, C. Guigne, C. Carpene, R. Burcelin, I. Castan-Laurell, P. Valet, Cell Metab. 8, 437 (2008)PubMedCrossRefGoogle Scholar
  67. 67.
    Y.C. Long, J.R. Zierath, J. Clin. Invest. 116, 1776 (2006)PubMedCrossRefGoogle Scholar
  68. 68.
    P. Yue, H. Jin, M. Aillaud, A.C. Deng, J. Azuma, T. Asagami, R.K. Kundu, G.M. Reaven, T. Quertermous, P.S. Tsao, Am. J. Physiol. Endocrinol. Metab. 298, E59 (2010)PubMedCrossRefGoogle Scholar
  69. 69.
    S. Zhu, F. Sun, W. Li, Y. Cao, C. Wang, Y. Wang, D. Liang, R. Zhang, S. Zhang, H. Wang, F. Cao, Mol. Cell. Biochem. 353, 305 (2011)PubMedCrossRefGoogle Scholar
  70. 70.
    K. Higuchi, T. Masaki, K. Gotoh, S. Chiba, I. Katsuragi, K. Tanaka, T. Kakuma, H. Yoshimatsu, Endocrinology 148, 2690 (2007)PubMedCrossRefGoogle Scholar
  71. 71.
    B.C. Frier, D.B. Williams, D.C. Wright, Am. J. Physiol. Regul. Integr. Comp. Physiol. 297, R1761 (2009)PubMedCrossRefGoogle Scholar
  72. 72.
    L.E. Wright, A.E. Brandon, A.J. Hoy, G.B. Forsberg, C.J. Lelliott, J. Reznick, L. Lofgren, J. Oscarsson, M. Stromstedt, G.J. Cooney, N. Turner, Diabetologia 54, 1417 (2011)PubMedCrossRefGoogle Scholar
  73. 73.
    Yamamoto, T., Habata, Y., Matsumoto, Y., Yasuhara, Y., Hashimoto, T., Hamajyo, H., Anayama, H., Fujii, R., Fuse, H., Shintani, Y., Mori, M.: Apelin-transgenic mice exhibit a resistance against diet-induced obesity by increasing vascular mass and mitochondrial biogenesis in skeletal muscle. Biochim. Biophys. Acta. (2011). doi:10.1016/j.bbagen.2011.05.004
  74. 74.
    P. Yue, H. Jin, S. Xu, M. Aillaud, A.C. Deng, J. Azuma, R.K. Kundu, G.M. Reaven, T. Quertermous, P.S. Tsao, Endocrinology 152, 59 (2011)PubMedCrossRefGoogle Scholar
  75. 75.
    Attané, C., Guzman-Riuz, R., Le Gonidec S., Béziaire, V., Daviaud, D., Dray, C., Ruiz-Gayo, M., Valet, P., Castan-laurell, I.: Chronic apelin treatment effects on lipid metabolism in wild type and insulin-resistant mice. Diabetologia 52(Suppl), S20 (2009)Google Scholar
  76. 76.
    A. Reaux, N. De Mota, I. Skultetyova, Z. Lenkei, S. El Messari, K. Gallatz, P. Corvol, M. Palkovits, C. Llorens-Cortes, J. Neurochem. 77, 1085 (2001)PubMedCrossRefGoogle Scholar
  77. 77.
    D. Sunter, A.K. Hewson, S.L. Dickson, Neurosci. Lett. 353, 1 (2003)PubMedCrossRefGoogle Scholar
  78. 78.
    M. O’Shea, M.J. Hansen, K. Tatemoto, M.J. Morris, Nutr. Neurosci. 6, 163 (2003)PubMedCrossRefGoogle Scholar
  79. 79.
    S. Taheri, K. Murphy, M. Cohen, E. Sujkovic, A. Kennedy, W. Dhillo, C. Dakin, A. Sajedi, M. Ghatei, S. Bloom, Biochem. Biophys. Res. Commun. 291, 1208 (2002)PubMedCrossRefGoogle Scholar
  80. 80.
    K.J. Clarke, K.W. Whitaker, T.M. Reyes, J. Neuroendocrinol. 21, 83 (2009)PubMedCrossRefGoogle Scholar
  81. 81.
    M. Jaszberenyi, E. Bujdoso, G. Telegdy, Neuroscience 129, 811 (2004)PubMedCrossRefGoogle Scholar
  82. 82.
    A. Valle, N. Hoggard, A.C. Adams, P. Roca, J.R. Speakman, J. Neuroendocrinol. 20, 79 (2008)PubMedGoogle Scholar
  83. 83.
    Duparc, T., Colom, A., Cani, P.D., Massaly, N., Rastrelli, S., Drougard, A., Le Gonidec, S., Mouledous, L., Frances, B., Leclercq, I., Llorens-Cortes, C., Pospisilik, J.A., Delzenne, N.M., Valet, P., Castan-Laurell, I., Knauf, C.: Central apelin controls glucose homeostasis via a nitric oxide-dependent pathway in mice. Antioxid Redox Signal. (2011). doi:10.1089/ars.2010.3454
  84. 84.
    G. Barnes, A.G. Japp, D.E. Newby, Heart 96, 1011 (2010)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Isabelle Castan-Laurell
    • 1
  • Cédric Dray
    • 1
  • Camille Attané
    • 1
  • Thibaut Duparc
    • 1
  • Claude Knauf
    • 1
  • Philippe Valet
    • 1
  1. 1.UMR 1048 INSERM, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC)/Université Paul SabatierToulouse Cedex 4France

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