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Regenerative approaches to preserve pancreatic β-cell mass and function in diabetes pathogenesis

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Abstract

In both type 1 diabetes (T1D) and type 2 diabetes (T2D), there is a substantial β-cell mass loss. Residual β-cell mass is susceptible to cellular damage because of specific pancreatic β-cell characteristics. β cells have a low proliferation rate, being in human adults almost zero and a low antioxidant system that makes β cells susceptible to oxidative stress and increases their vulnerability to cell destruction. Different strategies have been addressed to preserve pancreatic β-cell residual mass and function in patients with diabetes. However, the effect of many compounds proposed in rodent models to trigger β-cell replication has different results in human β cells. In this review, scientific evidence of β-cell of two major regenerative approaches has been gathered. Regeneration proceedings for pancreatic β cells are promising and could improve β-cell proliferation capacity and contribute to the conservation of mature β-cell phenotypic characteristics. This evidence supports the notion that regenerative medicine could be a helpful strategy to yield amelioration of T1D and T2D pathogenesis.

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References

  1. A. Pisania, G.C. Weir, J.J. O’Neil, A. Omer, V. Tchipashvili, J. Lei et al. Quantitative analysis of cell composition and purity of human pancreatic islet preparations. Lab. Investig. 90, 1661–75 (2011). https://doi.org/10.1038/labinvest.2010.124.Quantitative

    Article  Google Scholar 

  2. H.I. Marrif, S.I. Al-Sunousi, Pancreatic β cell mass death. Front. Pharmacol. 7, 83 (2016). https://doi.org/10.3389/fphar.2016.00083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. B.E. Gregg, P.C. Moore, D. Demozay, B.A. Hall, M. Li, A. Husain et al. Formation of a human β-cell population within pancreatic islets is set early in life. J. Clin. Endocrinol. Metab. 97, 3197–206 (2012). https://doi.org/10.1210/jc.2012-1206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. I. Cozar-Castellano, N. Fiaschi-Taesch, T.A. Bigatel, K.K. Takane, A. García-Ocaña, R. Vasavada et al. Molecular control of cell cycle progression in the pancreatic β-cell. Endocr. Rev. 27, 356–70 (2006). https://doi.org/10.1210/er.2006-0004

    Article  CAS  PubMed  Google Scholar 

  5. Y. Dor, J. Brown, O.I. Martinez, D.A. Melton, Adult pancreatic β-cell are formed by self-duplication rather than stem-cell differentiation. Nature 429, 41–6 (2004)

    Article  CAS  Google Scholar 

  6. I. Swenne, Effects of aging on the regenerative capacity of the pancreatic β-cell of the rat. Diabetes 32, 14–9 (1983)

    Article  CAS  Google Scholar 

  7. R.N. Kulkarni, E.-B. Mizrachi, A. García-Ocaña, A.F. Stewart, Human β-cell proliferation and intracellular signaling driving in the dark without a road map. Diabetes 61, 2205–13 (2012). https://doi.org/10.2337/db12-0018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. T. Mezza, R.N. Kulkarni, The regulation of pre- and post-maturational plasticity of mammalian islet cell mass. Diabetologia 57, 1291–303 (2014). https://doi.org/10.1007/s00125-014-3251-7

    Article  PubMed  Google Scholar 

  9. N. Fiaschi-Taesch, T.A. Bigatel, B. Sicari, K.K. Takane, F. Salim, S. Velazquez-Garcia et al. Survey of the human pancreatic β-cell G1/S proteome reveals a potential therapeutic role for Cdk-6 and cyclin D1 in enhancing human β-cell replication and function in vivo. Diabetes 58, 882–93 (2009). https://doi.org/10.2337/db08-0631.N.F.-T

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. L.U.C. Bouwens, I. Rooman, Regulation of pancreatic beta-cell mass. Physiol. Rev. 85, 1255–70 (2005). https://doi.org/10.1152/physrev.00025.2004

    Article  CAS  PubMed  Google Scholar 

  11. B. Reusens, C. Remacle, Programming of the endocrine pancreas by the early nutritional environment. Int J. Biochem Cell Biol. 38, 913–22 (2006). https://doi.org/10.1016/j.biocel.2005.10.012

    Article  CAS  PubMed  Google Scholar 

  12. D.J. Hill, Development of the endocrine pancreas. Rev. Endocr. Metab. Disord. 6, 229–38 (2005). https://doi.org/10.1016/B978-0-323-18907-1.00030-5

    Article  PubMed  Google Scholar 

  13. Q. Zhou, D.A. Melton, Pancreas regeneration. Nature 557, 351–8 (2018). https://doi.org/10.1038/s41586-018-0088-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. T.M. Nordmann, E. Dror, F. Schulze, S. Traub, E. Berishvili, C. Barbie et al. The role of inflammation in β-cell dedifferentiation. Sci. Rep. 2017:6285. https://doi.org/10.1038/s41598-017-06731-w.

  15. C. Ackeifi, P. Wang, E. Karakose, J.E.M. Fox, B.J. González, H. Liu et al. GLP-1 receptor agonists synergize with DYRK1A inhibitors to potentiate functional human β-cell regeneration. Sci. Transl. Med 12, eaaw9996 (2020)

    Article  CAS  Google Scholar 

  16. D. Saunders, A.C. Powers, Replicative capacity of β-cells and type 1 diabetes. J. Autoimmun. 71, 59–68 (2016). https://doi.org/10.1016/j.jaut.2016.03.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. E. Dirice, D. Walpita, A. Vetere, B.C. Meier, S. Kahraman, J. Hu et al. Inhibition of DYRK1A stimulates human β-cell proliferation. Diabetes 65, 1660–71 (2016). https://doi.org/10.2337/db15-1127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. C. Ackeifi, E. Swartz, K. Kumar, H. Liu, S. Chalada, E. Karakose et al. Pharmacologic and genetic approaches define human pancreatic β cell mitogenic targets of DYRK1A inhibitors. JCI Insight 5, e132594 (2020)

    Article  Google Scholar 

  19. P. Wang, E. Karakose, H. Liu, E. Swartz, V. Zlatanic, J. Wilson et al. Combined inhibition of DYRK1A, SMAD and trithorax pathways synergizes to induce robust replication in adult human beta cells. Cell Metab. 29, 638–52 (2020). https://doi.org/10.1016/j.cmet.2018.12.005.Combined

    Article  Google Scholar 

  20. P. Wang, J. Alvarez-Perez, D.P. Felsenfeld, S. Sivendran, A. Bender, A. Kumar et al. Induction of human pancreatic beta cell replication by inhibitors of dual specificity tyrosine regulated kinase. Nat. Med. 21, 383–8 (2015). https://doi.org/10.1038/nm.3820.Induction

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. E. Karakose, C. Ackeifi, P. Wang, A.F. Stewart, Advances in drug discovery for human beta cell regeneration. Diabetologia 61, 1693–9 (2018). https://doi.org/10.1007/s00125-018-4639-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Y. Gwack, S. Sharma, J. Nardone, B. Tanasa, A. Iuga, S. Srikanth et al. A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT. Nature 441, 646–50 (2006). https://doi.org/10.1038/nature04631

    Article  CAS  PubMed  Google Scholar 

  23. J. Shirakawa, R.N. Kulkarni, Novel factors modulating human β-cell proliferation. Diabetes Obes. Metab. 18, 71–7 (2017). https://doi.org/10.1111/dom.12731.Novel

    Article  Google Scholar 

  24. W.R. Goodyer, X. Gu, Y. Liu, R. Bottino, G.R. Crabtree, S.K. Kim, Neonatal β cell development in mice and humans is regulated by calcineurin/NFAT. Dev. Cell 23, 21–34 (2012). https://doi.org/10.1016/j.devcel.2012.05.014.Neonatal

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. W. Shen, B. Taylor, Q. Jin, S. Meeusen, Y. Zhang, A. Kamireddy et al. Inhibition of DYRK1A and GSK3B induces human β-cell proliferation. Nat. Commun. 6, 8372 (2015). https://doi.org/10.1038/ncomms9372

    Article  CAS  PubMed  Google Scholar 

  26. K.I. Aamodt, R. Aramandla, J.J. Brown, N. Fiaschi-Taesch, P. Wang, A.F. Stewart et al. Development of a reliable automated screening system to identify small molecules and biologics that promote human β-cell regeneration. Am. J. Physiol. Endocrinol. Metab. 311, E859–68 (2016). https://doi.org/10.1152/ajpendo.00515.2015

    Article  PubMed  PubMed Central  Google Scholar 

  27. S. Dhawan, E. Dirice, R.N. Kulkarni, A. Bhushan, Inhibition of TGF-β signaling promotes human pancreatic β-cell replication. Diabetes 65, 1208–18 (2016). https://doi.org/10.2337/db15-1331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. G. Basile, R.N. Kulkarni, N.G. Morgan, How, when, and where do human β-cells regenerate? Curr. Diab Rep. 19, 48 (2020). https://doi.org/10.1007/s11892-019-1176-8.How

    Article  Google Scholar 

  29. Y. Nakagawa, T. Suzuki, H. Ishii, A. Ogata, D. Nakae, Mitochondrial dysfunction and biotransformation of β-carboline alkaloids, harmine and harmaline, on isolated rat hepatocytes. Chem. Biol. Interact. 188, 393–403 (2010). https://doi.org/10.1016/j.cbi.2010.09.004

    Article  CAS  PubMed  Google Scholar 

  30. H. Waki, K.W. Park, N. Mitro, L. Pei, R. Damoiseaux, D.C. Wilpitz et al. The small molecule harmine is an antidiabetic cell-type-specific regulator of PPAR g expression. Cell Metab. 5, 357–70 (2007). https://doi.org/10.1016/j.cmet.2007.03.010

    Article  CAS  PubMed  Google Scholar 

  31. B. Khor, J.D. Gagnon, G. Goel, M.I. Roche, K.L. Conway, K. Tran et al. The kinase DYRK1A reciprocally regulates the differentiation of Th17 and regulatory T cells. Elife 4, e05920 (2015). https://doi.org/10.7554/eLife.05920

    Article  PubMed Central  Google Scholar 

  32. D. Kondoh, S. Yamamoto, T. Tomita, K. Miyazaki, N. Itoh, Y. Yasumoto et al. Harmine lengthens circadian period of the mammalian molecular clock in the suprachiasmatic nucleus. Biol. Pharm. Bull. 37, 1422–7 (2014)

    Article  CAS  Google Scholar 

  33. H.E. Hohmeier, L. Zhang, B. Taylor, S. Stephens, D. Lu, P. Mcnamara et al. Identification of a small molecule that stimulates human β-cell proliferation and insulin secretion, and protects against cytotoxic stress in rat insulinoma cells. PLoS ONE 15, e0224344 (2020). https://doi.org/10.1371/journal.pone.0224344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Y. Li, B. Hao, Structural basis of dimerization-dependent ubiquitination by the SCF Fbx4 ubiquitin ligase. J. Biol. Chem. 285, 13896–906 (2010). https://doi.org/10.1074/jbc.M110.111518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. S. Tiwari, C. Roel, T. Mansoor, R. Wills, N. Perianayagam, P. Wang et al. Definition of a Skp2-c-Myc Pathway to Expand Human Beta-cells. Sci. Rep. 6, 28461 (2016). https://doi.org/10.1038/srep28461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. P.P. Khin, J.H. Lee, H.S. Jun, A brief review of the mechanisms of β-cell dedifferentiation in type 2 diabetes. Nutrients 2021;13. https://doi.org/10.3390/nu13051593.

  37. O. Friedman-Mazursky, R. Elkon, S. Efrat, Redifferentiation of expanded human islet β cells by inhibition of ARX. Sci. Rep. 6, 20698 (2016). https://doi.org/10.1038/srep20698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. J. Zhang, F. Liu, The De-, Re-, and trans-differentiation of β-cells: Regulation and function. Semin Cell Dev. Biol. 103, 68–75 (2020). https://doi.org/10.1016/j.semcdb.2020.01.003

    Article  PubMed  Google Scholar 

  39. G. Domínguez Gutiérrez, A.S. Bender, V. Cirulli, T.L. Mastracci, S.M. Kelly, A. Tsirigos et al. Pancreatic β cell identity requires continual repression of non–β cell programs. J. Clin. Investig 127, 244–59 (2017). https://doi.org/10.1172/JCI88017.NEUROD1

    Article  Google Scholar 

  40. M. Bensellam, J.C. Jonas, D.R. Laybutt, Mechanisms of β-cell dedifferentiation in diabetes: Recent findings and future research directions. J. Endocrinol. 236, R109–43 (2018). https://doi.org/10.1530/JOE-17-0516

    Article  PubMed  Google Scholar 

  41. Sachs S., Bastidas-Ponce A., Tritschler S., Bakhti M., Böttcher A., Sánchez-Garrido M.A., et al. Targeted Pharmacological Therapy Restores β-Cell Function for Diabetes Remission. 2 (Springer US, 2020). https://doi.org/10.1038/s42255-020-0171-3.

  42. W. Zhiyu, N.W. York, C.G. Nichols, M.S. Remedi, Pancreatic β-cell dedifferentiation in diabetes and re-differentiation following insulin therapy. Cell Metab. 19, 872–82 (2014). https://doi.org/10.1016/j.cmet.2014.03.010.Pancreatic

    Article  Google Scholar 

  43. X.N. Téllez, M. Vilaseca, Y. Martí, A. Pla, E. Montanya, β-Cell dedifferentiation, reduced duct cell plasticity, and impaired β-cell mass regeneration in middle-aged rats. Am. J. Physiol. Endocrinol. Metab. 311, E554–63 (2016). https://doi.org/10.1152/ajpendo.00502.2015

    Article  PubMed  Google Scholar 

  44. C. Talchai, S. Xuan, H.V. Lin, L. Sussel, D. Accili, Pancreatic β-cell dedifferentiation as mechanism of diabetic β-cell failure. Cell 150, 1223–34 (2012). https://doi.org/10.1016/j.cell.2012.07.029.Pancreatic

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Y. Bar, H.A. Russ, S. Knoller, L. Ouziel-Yahalom, E. Shimon, HES-1 is involved in adaptation of adult human β-cells to proliferation in vitro. Diabetes 57, 2413–20 (2008). https://doi.org/10.2337/db07-1323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. S. Efrat, Mechanisms of adult human β-cell in vitro dedifferentiation and redifferentiation. Diabetes Obes. Metab. 18, 97–101 (2016). https://doi.org/10.1111/dom.12724

    Article  PubMed  Google Scholar 

  47. A. Lenz, G. Toren-Haritan, S. Efrat, Redifferentiation of adult human β cells expanded in vitro by inhibition of the WNT pathway. PLoS ONE 9, e112914 (2014). https://doi.org/10.1371/journal.pone.0112914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. M. Bakhti, A. Böttcher, H. Lickert, Modelling the endocrine pancreas in health and disease. Nat. Rev. Endocrinol. 15, 155–71 (2019). https://doi.org/10.1038/s41574-018-0132-z

    Article  CAS  PubMed  Google Scholar 

  49. W.L. Qiu, Y.W. Zhang, Y. Feng, L.C. Li, L. Yang, C.R. Xu, Deciphering pancreatic islet β cell and α cell maturation pathways and characteristic features at the single-cell level. Cell Metab. 25, 1194–1205.e4 (2017). https://doi.org/10.1016/j.cmet.2017.04.003

    Article  CAS  PubMed  Google Scholar 

  50. C. Zeng, F. Mulas, Y. Sui, T. Guan, N. Miller, F. Liu et al. Pseudotemporal ordering of single cells reveals metabolic control of postnatal beta-cell proliferation. Cell Metab. 25, 1160–75 (2017).https://doi.org/10.1016/j.cmet.2017.04.014.Pseudotemporal

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. J. Sun, Q. Ni, J. Xie, M. Xu, J. Zhang, J. Kuang et al. β-cell dedifferentiation in patients With T2D With adequate glucose control and nondiabetic chronic pancreatitis. J. Clin. Endocrinol. Metab. 104, 83–94 (2019). https://doi.org/10.1210/jc.2018-00968

    Article  PubMed  Google Scholar 

  52. W. Ying, Y.S. Lee, Y. Dong, J.S. Seidman, M. Yang, R. Isaac et al. Expansion of islet-resident macrophages leads to inflammation affecting β cell proliferation and function in obesity. Cell Metab. 29, 457–474.e5 (2019). https://doi.org/10.1016/j.cmet.2018.12.003

    Article  CAS  PubMed  Google Scholar 

  53. W. He, T. Yuan, K. Maedler, Macrophage-associated pro-inflammatory state in human islets from obese individuals. Nutr. Diabetes 9, 36 (2019). https://doi.org/10.1038/s41387-019-0103-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. M. Ghodsi, B. Larijani, A.A. Keshtkar, E. Nasli-Esfahani, S. Alatab, M.R. Mohajeri-Tehrani, Mechanisms involved in altered bone metabolism in diabetes: a narrative review. J. Diabetes Metab. Disord. 15, 52 (2016). https://doi.org/10.1186/s40200-016-0275-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. R.A. DeFronzo, E. Ferrannini, L. Groop, R.R. Henry, W.H. Herman, J.J. Holst et al. Type 2 diabetes mellitus. Nat. Rev. Dis. Prim. 1, 1–22 (2015). https://doi.org/10.1038/s41574-019-0286-3

    Article  Google Scholar 

  56. S. Efrat, Beta-cell dedifferentiation in type 2 diabetes: concise review. Transl. Clin. Res. 37, 1267–72 (2019). https://doi.org/10.1002/stem.3059

    Article  Google Scholar 

  57. F. Han, X. Li, J. Yang, H. Liu, Y. Zhang, X. Yang et al. Salsalate prevents β-cell dedifferentiation in OLETF rats with type 2 diabetes through Notch1 pathway. Aging Dis. 10, 719–30 (2019). https://doi.org/10.14336/AD.2018.1221

    Article  PubMed  PubMed Central  Google Scholar 

  58. Y.S. Oh, S. Shin, Y.J. Lee, E.H. Kim, H.S. Jun, Betacellulin-induced beta cell proliferation and regeneration is mediated by activation of ErbB-1 and ErbB-2 receptors. PLoS ONE. 2011;6. https://doi.org/10.1371/journal.pone.0023894.

  59. S. Shin, N. Li, N. Kobayashi, J.W. Yoon, H.S. Jun, Remission of diabetes by β-cell regeneration in diabetic mice treated with a recombinant adenovirus expressing Betacellulin. Mol. Ther. 16, 854–61 (2008). https://doi.org/10.1038/mt.2008.22

    Article  CAS  PubMed  Google Scholar 

  60. H. Kojima, M. Fujimiya, K. Matsumura, P. Younan, H. Imaeda, M. Maeda et al. NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nat. Med. 9, 596–603 (2003). https://doi.org/10.1038/nm867

    Article  CAS  PubMed  Google Scholar 

  61. L. Li, M. Seno, H. Yamada, I. Kojima, Betacellulin improves glucose metabolism by promoting conversion of intraislet precursor cells to β-cells in streptozotocin-treated mice. Am. J. Physiol. Endocrinol. Metab. 285, 577–83 (2003). https://doi.org/10.1152/ajpendo.00120.2003

    Article  Google Scholar 

  62. L. Ouziel-Yahalom, M. Zalzman, L. Anker-kitai, S. Knoller, Y. Bar, M. Glandt et al. Expansion and redifferentiation of adult human pancreatic islet cells. Biochem. Biophys. Res. Commun. 341, 291–8 (2006). https://doi.org/10.1016/j.bbrc.2005.12.187

    Article  CAS  PubMed  Google Scholar 

  63. Y.S. Lee, G.J. Song, H.S. Jun, Betacellulin-induced α-cell proliferation is mediated by ErbB3 and ErbB4, and may contribute to β-cell regeneration. Front Cell Dev. Biol. 8, 1–11 (2021). https://doi.org/10.3389/fcell.2020.605110

    Article  CAS  Google Scholar 

  64. M.Y. Song, U.J. Bae, K.Y. Jang, B.H. Park, Transplantation of betacellulin-transduced islets improves glucose intolerance in diabetic mice. Exp. Mol. Med. 46, e98–8 (2014). https://doi.org/10.1038/emm.2014.24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. H.A. Russ, E. Sintov, L. Anker-Kitai, O. Friedman, A. Lenz, G. Toren et al. Insulin-producing cells generated from dedifferentiated human pancreatic beta cells expanded in vitro. PLoS ONE 6, e25566 (2011). https://doi.org/10.1371/journal.pone.0025566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. R.P. Robertson, L.K. Olson, H.-J. Zhang, Differentiating glucose toxicity from glucose desensitization: A new message from the insulin gene. Diabetes 43, 1085–9 (1994). https://doi.org/10.2337/diab.43.9.1085

    Article  CAS  PubMed  Google Scholar 

  67. E. Sintov, G. Nathan, S. Knoller, M. Pasmanik-Chor, H.A. Russ, E. Shimon, Inhibition of ZEB1 expression induces redifferentiation of adult human β cells expanded in vitro. Sci. Rep. 5, 13024 (2015). https://doi.org/10.1038/srep13024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. B. Finan, B. Yang, N. Ottaway, K. Stemmer, T.D. Müller, C.-X. Yi et al. Targeted estrogen delivery reverses the metabolic syndrome. Nat. Med. 18, 1847–56 (2012). https://doi.org/10.1038/nm.3009.Targeted

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. F. Mauvais-Jarvis, C. Le May, J.P. Tiano, S. Liu, G. Kilic-Berkmen, J.H. Kim, The role of estrogens in pancreatic islet physiopathology. Adv. Exp. Med Biol. 1043, 385–99 (2017). https://doi.org/10.1007/978-3-319-70178-3_18

    Article  CAS  PubMed  Google Scholar 

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    Maria Fernanda Desentis-Desentis

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Desentis-Desentis, M.F. Regenerative approaches to preserve pancreatic β-cell mass and function in diabetes pathogenesis. Endocrine 75, 338–350 (2022). https://doi.org/10.1007/s12020-021-02941-5

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