Table of Contents Author Guidelines Submit a Manuscript
Journal of Diabetes Research
Volume 2016, Article ID 4860595, 7 pages
http://dx.doi.org/10.1155/2016/4860595
Review Article

The Rise and the Fall of Betatrophin/ANGPTL8 as an Inducer of β-Cell Proliferation

1Biochemistry and Molecular Biology Unit, Dasman Diabetes Institute, Kuwait City, Kuwait
2Research Division, Dasman Diabetes Institute, Kuwait City, Kuwait

Received 15 June 2016; Revised 16 August 2016; Accepted 17 August 2016

Academic Editor: Daisuke Yabe

Copyright © 2016 Mohamed Abu-Farha et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. A. DeFronzo, E. Ferrannini, L. Groop et al., “Type 2 diabetes mellitus,” Nature Reviews Disease Primers, vol. 1, Article ID 15019, 2015. View at Publisher · View at Google Scholar
  2. J. Tuomilehto, J. Lindström, J. G. Eriksson et al., “Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance,” The New England Journal of Medicine, vol. 344, no. 18, pp. 1343–1350, 2001. View at Publisher · View at Google Scholar
  3. S. O'Rahilly, “Human obesity and insulin resistance: lessons from experiments of nature,” Biochemical Society Transactions, vol. 35, part 1, pp. 33–36, 2007. View at Publisher · View at Google Scholar
  4. A. M. Ackermann and M. Gannon, “Molecular regulation of pancreatic beta-cell mass development, maintenance, and expansion,” Journal of Molecular Endocrinology, vol. 38, no. 1-2, pp. 193–206, 2007. View at Publisher · View at Google Scholar
  5. C. Bernard-Kargar and A. Ktorza, “Endocrine pancreas plasticity under physiological and pathological conditions,” Diabetes, vol. 50, supplement 1, pp. S30–S35, 2001. View at Publisher · View at Google Scholar · View at Scopus
  6. J. Petrik, B. Reusens, E. Arany et al., “A low protein diet alters the balance of islet cell replication and apoptosis in the fetal and neonatal rat and is associated with a reduced pancreatic expression of insulin-like growth factor-II,” Endocrinology, vol. 140, no. 10, pp. 4861–4873, 1999. View at Publisher · View at Google Scholar · View at Scopus
  7. E. Montanya, V. Nacher, M. Biarnes, and J. Soler, “Linear correlation between beta-cell mass and body weight throughout the lifespan in Lewis rats: role of beta-cell hyperplasia and hypertrophy,” Diabetes, vol. 49, no. 8, pp. 1341–1346, 2000. View at Publisher · View at Google Scholar · View at Scopus
  8. R. L. Sorenson, T. C. Brelje, and C. Roth, “Effects of steroid and lactogenic hormones on islets of langerhans: a new hypothesis for the role of pregnancy steroids in the adaptation of islets to pregnancy,” Endocrinology, vol. 133, no. 5, pp. 2227–2234, 1993. View at Google Scholar · View at Scopus
  9. T. C. Brelje, D. W. Scharp, P. E. Lacy et al., “Effect of homologous placental lactogens, prolactins, and growth hormones on islet B-cell division and insulin secretion in rat, mouse, and human islets: implication for placental lactogen regulation of islet function during pregnancy,” Endocrinology, vol. 132, no. 2, pp. 879–887, 1993. View at Google Scholar · View at Scopus
  10. J. Domínguez-Bendala, L. Inverardi, and C. Ricordi, “Regeneration of pancreatic beta-cell mass for the treatment of diabetes,” Expert Opinion on Biological Therapy, vol. 12, no. 6, pp. 731–741, 2012. View at Publisher · View at Google Scholar
  11. A. K. Linnemann, M. Baan, and D. B. Davis, “Pancreatic beta-cell proliferation in obesity,” Advances in Nutrition, vol. 5, no. 3, pp. 278–288, 2014. View at Publisher · View at Google Scholar
  12. J. J. Meier, A. E. Butler, Y. Saisho et al., “β-cell replication is the primary mechanism subserving the postnatal expansion of β-cell mass in humans,” Diabetes, vol. 57, no. 6, pp. 1584–1594, 2008. View at Publisher · View at Google Scholar
  13. Y. Dor, J. Brown, O. I. Martinez, and D. A. Melton, “Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation,” Nature, vol. 429, no. 6987, pp. 41–46, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. S. Georgia and A. Bhushan, “β cell replication is the primary mechanism for maintaining postnatal β cell mass,” Journal of Clinical Investigation, vol. 114, no. 7, pp. 963–968, 2004. View at Publisher · View at Google Scholar
  15. T. Nir, D. A. Melton, and Y. Dor, “Recovery from diabetes in mice by beta cell regeneration,” The Journal of Clinical Investigation, vol. 117, no. 9, pp. 2553–2561, 2007. View at Publisher · View at Google Scholar
  16. P. Wang, N. M. Fiaschi-Taesch, R. C. Vasavada, D. K. Scott, A. García-Ocaña, and A. F. Stewart, “Diabetes mellitus—advances and challenges in human β-cell proliferation,” Nature Reviews Endocrinology, vol. 11, no. 4, pp. 201–212, 2015. View at Publisher · View at Google Scholar
  17. D. Saunders and A. C. Powers, “Replicative capacity of β-cells and type 1 diabetes,” Journal of Autoimmunity, vol. 71, pp. 59–68, 2016. View at Publisher · View at Google Scholar
  18. S. Bonner-Weir, W. C. Li, L. Ouziel-Yahalom, L. Guo, G. C. Weir, and A. Sharma, “β-cell growth and regeneration: replication is only part of the story,” Diabetes, vol. 59, no. 10, pp. 2340–2348, 2010. View at Publisher · View at Google Scholar
  19. K. Juhl, S. Bonner-Weir, and A. Sharma, “Regenerating pancreatic β-cells: plasticity of adult pancreatic cells and the feasibility of in-vivo neogenesis,” Current Opinion in Organ Transplantation, vol. 15, no. 1, pp. 79–85, 2010. View at Publisher · View at Google Scholar
  20. S. Bonner-Weir, L. Guo, W.-C. Li et al., “Islet neogenesis: a possible pathway for beta-cell replenishment,” Review of Diabetic Studies, vol. 9, no. 4, pp. 407–416, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Rovira, S. G. Scott, A. S. Liss, J. Jensen, S. P. Thayer, and S. D. Leach, “Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas,” Proceedings of the National Academy of Sciences, vol. 107, no. 1, pp. 75–80, 2010. View at Publisher · View at Google Scholar
  22. F. Delaspre, R. L. Beer, M. Rovira et al., “Centroacinar cells are progenitors that contribute to endocrine pancreas regeneration,” Diabetes, vol. 64, no. 10, pp. 3499–3509, 2015. View at Publisher · View at Google Scholar
  23. X. Xiao, Z. Chen, C. Shiota et al., “No evidence for β cell neogenesis in murine adult pancreas,” Journal of Clinical Investigation, vol. 123, no. 5, pp. 2207–2217, 2013. View at Publisher · View at Google Scholar
  24. M. M. Rankin, C. J. Wilbur, K. Rak, E. J. Shields, A. Granger, and J. A. Kushner, “β-Cells are not generated in pancreatic duct ligation-induced injury in adult mice,” Diabetes, vol. 62, no. 5, pp. 1634–1645, 2013. View at Publisher · View at Google Scholar
  25. C. Cavelti-Weder, M. Shtessel, J. E. Reuss et al., “Pancreatic duct ligation after almost complete β-cell loss: exocrine regeneration but no evidence of β-cell regeneration,” Endocrinology, vol. 154, no. 12, pp. 4493–4502, 2013. View at Publisher · View at Google Scholar · View at Scopus
  26. F. Thorel, V. Népote, I. Avril et al., “Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss,” Nature, vol. 464, no. 7292, pp. 1149–1154, 2010. View at Publisher · View at Google Scholar
  27. C. Talchai, S. Xuan, H. V. Lin, L. Sussel, and D. Accili, “Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure,” Cell, vol. 150, no. 6, pp. 1223–1234, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. P. Collombat and A. Mansouri, “Turning on the β-cell identity in the pancreas,” Cell Cycle, vol. 8, no. 21, pp. 3450–3451, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Kordowich, A. Mansouri, and P. Collombat, “Reprogramming into pancreatic endocrine cells based on developmental cues,” Molecular and Cellular Endocrinology, vol. 315, no. 1-2, pp. 11–18, 2010. View at Publisher · View at Google Scholar
  30. L. Ye, M. A. Robertson, D. Hesselson, D. Y. Stainier, and R. M. Anderson, “Glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis,” Development, vol. 142, no. 8, pp. 1407–1417, 2015. View at Publisher · View at Google Scholar
  31. A. Mansouri, “Development and regeneration in the endocrine pancreas,” ISRN Endocrinology, vol. 2012, Article ID 640956, 12 pages, 2012. View at Publisher · View at Google Scholar
  32. R. Piran, S. H. Lee, C. R. Li, A. Charbono, L. M. Bradley, and F. Levine, “Pharmacological induction of pancreatic islet cell transdifferentiation: relevance to type I diabetes,” Cell Death and Disease, vol. 5, no. 7, Article ID e1357, 2014. View at Publisher · View at Google Scholar
  33. J. H. Nielsen, S. Linde, B. S. Welinder, N. Billestrup, and O. D. Madsen, “Growth hormone is a growth factor for the differentiated pancreatic β-cell,” Molecular Endocrinology, vol. 3, no. 1, pp. 165–173, 1989. View at Publisher · View at Google Scholar
  34. B. N. Friedrichsen, E. D. Galsgaard, J. H. Nielsen, and A. Møldrup, “Growth hormone- and prolactin-induced proliferation of insulinoma cells, INS-1, depends on activation of STAT5 (signal transducer and activator of transcription 5),” Molecular Endocrinology, vol. 15, no. 1, pp. 136–148, 2001. View at Publisher · View at Google Scholar · View at Scopus
  35. N. Billestrup and J. H. Nielsen, “The stimulatory effect of growth hormone, prolactin, and placental lactogen on β-cell proliferation is not mediated by insulin-like growth factor-I,” Endocrinology, vol. 129, no. 2, pp. 883–888, 1991. View at Publisher · View at Google Scholar · View at Scopus
  36. H. Kim, Y. Toyofuku, F. C. Lynn et al., “Serotonin regulates pancreatic beta cell mass during pregnancy,” Nature Medicine, vol. 16, no. 7, pp. 804–808, 2010. View at Publisher · View at Google Scholar
  37. J. Buteau, S. Foisy, E. Joly, and M. Prentki, “Glucagon-like peptide 1 induces pancreatic β-cell proliferation via transactivation of the epidermal growth factor receptor,” Diabetes, vol. 52, no. 1, pp. 124–132, 2003. View at Publisher · View at Google Scholar · View at Scopus
  38. S. R. Hügl, M. F. White, and C. J. Rhodes, “Insulin-like growth factor I (IGF-I)-stimulated pancreatic β-cell growth is glucose-dependent synergistic activation of insulin receptor substrate-mediated signal transduction pathways by glucose and IGF-I in INS- 1 cells,” The Journal of Biological Chemistry, vol. 273, no. 28, pp. 17771–17779, 1998. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. Huang and Y. Chang, “Regulation of pancreatic islet beta-cell mass by growth factor and hormone signaling,” Progress in Molecular Biology and Translational Science, vol. 121, pp. 321–349, 2014. View at Publisher · View at Google Scholar
  40. F. Zhang, A. Sjoholm, and Q. Zhang, “Growth hormone signaling in pancreatic β-cells—calcium handling regulated by growth hormone,” Molecular and Cellular Endocrinology, vol. 297, no. 1-2, pp. 50–57, 2009. View at Publisher · View at Google Scholar
  41. C. Widmann, E. Bürki, W. Dolci, and B. Thorens, “Signal transduction by the cloned glucagon-like peptide-1 receptor: comparison with signaling by the endogenous receptors of β cell lines,” Molecular Pharmacology, vol. 45, no. 5, pp. 1029–1035, 1994. View at Google Scholar · View at Scopus
  42. P. N. Nair, D. T. De Armond, M. L. Adamo, W. E. Strodel, and J. W. Freeman, “Aberrant expression and activation of insulin-like growth factor-1 receptor (IGF-1R) are mediated by an induction of IGF-1R promoter activity and stabilization of IGF-1R mRNA and contributes to growth factor independence and increased survival of the pancreatic cancer cell line MIA PaCa-2,” Oncogene, vol. 20, no. 57, pp. 8203–8214, 2001. View at Publisher · View at Google Scholar · View at Scopus
  43. M. Bando, H. Iwakura, H. Ariyasu et al., “Overexpression of intraislet ghrelin enhances β-cell proliferation after streptozotocin-induced β-cell injury in mice,” American Journal of Physiology—Endocrinology and Metabolism, vol. 305, no. 1, pp. E140–E148, 2013. View at Publisher · View at Google Scholar · View at Scopus
  44. R. Granata, F. Settanni, L. Biancone et al., “Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic β-cells and human islets: involvement of 3′,5′-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-kinase/Akt signaling,” Endocrinology, vol. 148, no. 2, pp. 512–529, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. Y. S. Oh, S. Shin, Y. Lee, E. H. Kim, H. Jun, and K. Maedler, “Betacellulin-induced beta cell proliferation and regeneration is mediated by activation of ErbB-1 and ErbB-2 receptors,” PLoS ONE, vol. 6, no. 8, Article ID e23894, 2011. View at Publisher · View at Google Scholar
  46. G. Ren, J. Y. Kim, and C. M. Smas, “Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism,” American Journal of Physiology. Endocrinology and Metabolism, vol. 303, no. 3, pp. E334–E351, 2012. View at Google Scholar
  47. R. Zhang and A. B. Abou-Samra, “Emerging roles of Lipasin as a critical lipid regulator,” Biochemical and Biophysical Research Communications, vol. 432, no. 3, pp. 401–405, 2013. View at Publisher · View at Google Scholar
  48. F. Quagliarini, Y. Wang, J. Kozlitina et al., “Atypical angiopoietin-like protein that regulates ANGPTL3,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 48, pp. 19751–19756, 2012. View at Publisher · View at Google Scholar
  49. P. Yi, J. Park, and D. Melton, “Betatrophin: a hormone that controls pancreatic β cell proliferation,” Cell, vol. 153, no. 4, pp. 747–758, 2013. View at Publisher · View at Google Scholar
  50. V. Gusarova, C. Alexa, E. Na et al., “ANGPTL8/betatrophin does not control pancreatic beta cell expansion,” Cell, vol. 159, no. 3, pp. 691–696, 2014. View at Publisher · View at Google Scholar
  51. D. Espes, J. Lau, and P. O. Carlsson, “Increased circulating levels of betatrophin in individuals with long-standing type 1 diabetes,” Diabetologia, vol. 57, no. 1, pp. 50–53, 2014. View at Publisher · View at Google Scholar
  52. M. Abu-Farha, J. Abubaker, I. Al-Khairi et al., “Higher plasma betatrophin/ANGPTL8 level in Type 2 Diabetes subjects does not correlate with blood glucose or insulin resistance,” Scientific Reports, vol. 5, article 10949, 2015. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Gomez-Ambrosi, E. Pascual, V. Catalan et al., “Circulating betatrophin concentrations are decreased in human obesity and type 2 diabetes,” The Journal of Clinical Endocrinology & Metabolism, vol. 99, no. 10, pp. E2004–E2009, 2014. View at Publisher · View at Google Scholar
  54. R. Zhang, “Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels,” Biochemical and Biophysical Research Communications, vol. 424, no. 4, pp. 786–792, 2012. View at Publisher · View at Google Scholar · View at Scopus
  55. Z. Fu, F. Yao, A. B. Abou-Samra, and R. Zhang, “Lipasin, thermoregulated in brown fat, is a novel but atypical member of the angiopoietin-like protein family,” Biochemical and Biophysical Research Communications, vol. 430, no. 3, pp. 1126–1131, 2013. View at Publisher · View at Google Scholar · View at Scopus
  56. M. Abu-Farha, M. Melhem, J. Abubaker, K. Behbehani, O. Alsmadi, and N. Elkum, “ANGPTL8/Betatrophin R59W variant is associated with higher glucose level in non-diabetic Arabs living in Kuwaits,” Lipids in Health and Disease, vol. 15, article 26, 2016. View at Publisher · View at Google Scholar · View at Scopus
  57. E. Kugelberg, “Diabetes: betatrophin—inducing β-cell expansion to treat diabetes mellitus?” Nature Reviews Endocrinology, vol. 9, no. 7, pp. 379–379, 2013. View at Publisher · View at Google Scholar
  58. H. Lickert, “Betatrophin fuels β cell proliferation: first step toward regenerative therapy?” Cell Metabolism, vol. 18, no. 1, pp. 5–6, 2013. View at Publisher · View at Google Scholar
  59. Y. Wang, F. Quagliarini, V. Gusarova et al., “Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis,” Proceedings of the National Academy of Sciences, vol. 110, no. 40, pp. 16109–16114, 2013. View at Publisher · View at Google Scholar
  60. Y. Jiao, J. Le Lay, M. Yu, A. Naji, and K. H. Kaestner, “Elevated mouse hepatic betatrophin expression does not increase human β-cell replication in the transplant setting,” Diabetes, vol. 63, no. 4, pp. 1283–1288, 2014. View at Publisher · View at Google Scholar
  61. A. F. Stewart, “Betatrophin versus bitter-trophin and the elephant in the room: time for a new normal in β-cell regeneration research,” Diabetes, vol. 63, no. 4, pp. 1198–1199, 2014. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Abu-Farha, J. Abubaker, F. Noronha et al., “Lack of associations between betatrophin/ANGPTL8 level and C-peptide in type 2 diabetic subjects,” Cardiovascular Diabetology, vol. 14, no. 1, article 112, 2015. View at Publisher · View at Google Scholar
  63. K. Guo, J. Lu, H. Yu et al., “Serum betatrophin concentrations are significantly increased in overweight but not in obese or type 2 diabetic individuals,” Obesity, vol. 23, no. 4, pp. 793–797, 2015. View at Publisher · View at Google Scholar
  64. H. Hu, W. Sun, S. Yu et al., “Increased circulating levels of betatrophin in newly diagnosed type 2 diabetic patients,” Diabetes Care, vol. 37, no. 10, pp. 2718–2722, 2014. View at Publisher · View at Google Scholar
  65. D. Espes, M. Martinell, and P. Carlsson, “Increased circulating betatrophin concentrations in patients with type 2 diabetes,” International Journal of Endocrinology, vol. 2014, 6 pages, 2014. View at Publisher · View at Google Scholar
  66. A. Fenzl, B. K. Itariu, L. Kosi et al., “Circulating betatrophin correlates with atherogenic lipid profiles but not with glucose and insulin levels in insulin-resistant individuals,” Diabetologia, vol. 57, no. 6, pp. 1204–1208, 2014. View at Publisher · View at Google Scholar · View at Scopus
  67. Z. Fu, F. Berhane, A. Fite, B. Seyoum, A. B. Abou-Samra, and R. Zhang, “Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity,” Scientific Reports, vol. 4, article 5013, 2014. View at Publisher · View at Google Scholar · View at Scopus
  68. X. Chen, P. Lu, W. He et al., “Circulating betatrophin levels are increased in patients with type 2 diabetes and associated with insulin resistance,” The Journal of Clinical Endocrinology & Metabolism, vol. 100, no. 1, pp. E96–E100, 2015. View at Publisher · View at Google Scholar
  69. A. R. Cox, C. J. Lam, C. W. Bonnyman, J. Chavez, J. S. Rios, and J. A. Kushner, “Angiopoietin-like protein 8 (ANGPTL8)/betatrophin overexpression does not increase beta cell proliferation in mice,” Diabetologia, vol. 58, no. 7, pp. 1523–1531, 2015. View at Publisher · View at Google Scholar · View at Scopus
  70. H. Yamada, T. Saito, A. Aoki et al., “Circulating betatrophin is elevated in patients with type 1 and type 2 diabetes,” Endocrine Journal, vol. 62, no. 5, pp. 417–421, 2015. View at Publisher · View at Google Scholar
  71. M. Abu-Farha, J. Abubaker, I. Al-Khairi et al., “Circulating angiopoietin-like protein 8 (betatrophin) association with HsCRP and metabolic syndrome,” Cardiovascular Diabetology, vol. 15, no. 1, article 25, 2016. View at Publisher · View at Google Scholar
  72. M. Abu-Farha, D. Sriraman, P. Cherian et al., “Circulating ANGPTL8/betatrophin is increased in obesity and reduced after exercise training,” PLoS ONE, vol. 11, no. 1, Article ID e0147367, 2016. View at Publisher · View at Google Scholar · View at Scopus
  73. S. Li, D. Liu, L. Li et al., “Circulating betatrophin in patients with type 2 diabetes: a meta-analysis,” Journal of Diabetes Research, vol. 2016, 9 pages, 2016. View at Publisher · View at Google Scholar
  74. O. Erol, H. Y. Ellidağ, H. Ayık, M. K. Özel, A. U. Derbent, and N. Yılmaz, “Evaluation of circulating betatrophin levels in gestational diabetes mellitus,” Gynecological Endocrinology, vol. 31, no. 8, pp. 652–656, 2015. View at Publisher · View at Google Scholar
  75. L. K. Trebotic, P. Klimek, A. Thomas et al., “Circulating betatrophin is strongly increased in pregnancy and gestational diabetes mellitus,” PLoS ONE, vol. 10, no. 9, Article ID e0136701, 2015. View at Publisher · View at Google Scholar · View at Scopus
  76. N. Wawrusiewicz-Kurylonek, B. Telejko, M. Kuzmicki et al., “Increased maternal and cord blood betatrophin in gestational diabetes,” PLoS ONE, vol. 10, no. 6, Article ID e0131171, 2015. View at Publisher · View at Google Scholar
  77. X. Xie, H. Gao, S. Wu et al., “Increased cord blood betatrophin levels in the offspring of mothers with gestational diabetes,” PLoS ONE, vol. 11, no. 5, Article ID e0155646, 2016. View at Publisher · View at Google Scholar
  78. Z. Fu, A. B. Abou-Samra, and R. Zhang, “An explanation for recent discrepancies in levels of human circulating betatrophin,” Diabetologia, vol. 57, no. 10, pp. 2232–2234, 2014. View at Publisher · View at Google Scholar
  79. G. Erbag, M. Eroglu, H. Turkon et al., “Relationship between betatrophin levels and metabolic parameters in patients with polycystic ovary syndrome,” Cellular and Molecular Biology, vol. 62, no. 5, pp. 20–24, 2016. View at Google Scholar