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Regeneration of Beta Cells by Inhibition of pro-Apoptotic Proteins through Phytocompound in STZ Induced Diabetic Albino Wistar Rats: In Vivo and In Silico Approach

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Structure and Health Effects of Natural Products on Diabetes Mellitus

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Abstract

Type 1 diabetes mellitus (T1DM) is due to severe insulin deficiency by loss of insulin-producing β-cells. Hence, induction of β-cell proliferation is a promising therapeutic strategy to regenerate β-cell mass. Both extrinsic (receptor-mediated) and intrinsic (mitochondria-driven) pathway constitutes the apoptotic pathway. Extrinsic pathway driven by external factors and mitochondria-driven intrinsic pathway are known to operate at a balance and regulate pro-apoptotic and anti-apoptotic proteins. Hence, there is a future hope for therapeutic application to slow or even prevent β-cell apoptosis in T1DM by inhibiting pro-apoptotic proteins employing natural phytocompounds. Among the several plants screened, Elephantopus scaber was found to have a remarkable anti-diabetic activity. Terpenoid, the bioactive phytocompound isolated from the mentioned plant was found to increase insulin and restore glucose homeostasis. Experimental analysis in STZ diabetic rats demonstrated an increase in insulin by regeneration of beta cells. However, the underlying mechanism of beta cell regeneration was analysed by inhibition of pro-apoptotic proteins. Thus, restoring pancreatic beta cell function by inhibiting pro-apoptotic proteins may be an effective strategical approach for the prevention and treatment of diabetes, which may open doors for establishing phytocompounds as operative anti-diabetics. Restoring insulin secretion by regenerating beta cells in STZ induced diabetic rats can be traced to the inhibition of pro-apoptotic proteins by phytocompound through in silico study.

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References

  1. Halimi S (2006) Diabetes in 2005 (Le diabete en 2005). Nephrol Ther 2(Suppl 1):S2–S7

    PubMed  Google Scholar 

  2. Kumar PJ, Clark M (2002) Diabetes mellitus and other disorders of metabolism. Clin Med 2:1069–1121

    Google Scholar 

  3. Wu C, Khan SA, Peng L-J, Lange AJ (2006) Roles for fructose-2,6-bisphosphate in the control of fuel metabolism: beyond its allosteric effects on glycolytic and gluconeogenic enzymes. In: Weber G, Weber CEF, Cocco L (eds) Advances in enzyme regulation, vol 46, proceedings, vol 46. Advances in enzyme regulation, pp 72–88. https://doi.org/10.1016/j.advenzreg.2006.01.010

    Chapter  Google Scholar 

  4. Kris-Etherton PM, Binkoski AE, Zhao G, Coval SM, Clemmer KF, Hecker KD, Jacques H, Etherton TD (2002) Dietary fat: assessing the evidence in support of a moderate-fat diet; the benchmark based on lipoprotein metabolism. Proc Nutr Soc 61(2):287–298. https://doi.org/10.1079/pns2002157

    Article  CAS  PubMed  Google Scholar 

  5. Kaji M, Nomura M, Tamura Y, Ito S (2007) Relationships between insulin resistance, blood glucose levels and gastric motility: an electrogastrography and external ultrasonography study. J Med Invest JMI 54(1–2):168–176. https://doi.org/10.2152/jmi.54.168

    Article  PubMed  Google Scholar 

  6. Ogata H, Tokuyama K, Nagasaka S, Ando A, Kusaka I, Sato N, Goto A, Ishibashi S, Kiyono K, Struzik ZR, Yamamoto Y (2007) Long-range correlated glucose fluctuations in diabetes. Methods Inf Med 46(2):222–226

    Article  CAS  PubMed  Google Scholar 

  7. Raccah D (2006) Importance of blood glucose management in the multifactorial approach of absolute cardiovascular risk in type 2 diabetes: the lessons from the Steno 2 study. Diabetes Metab 32(2):2S48–42S51. https://doi.org/10.1016/s1262-3636(06)70486-4

    Article  PubMed  Google Scholar 

  8. Dunne MJ, Cosgrove KE, Shepherd RM, Aynsley-Green A, Lindley KJ (2004) Hyperinsulinism in infancy: from basic science to clinical disease. Physiol Rev 84(1):239–275. https://doi.org/10.1152/physrev.00022.2003

    Article  CAS  PubMed  Google Scholar 

  9. Yajnik CS (2001) The insulin resistance epidemic in India: fetal origins, later lifestyle, or both? Nutr Rev 59:1):1–1):9

    PubMed  Google Scholar 

  10. Daneman D (2006) Type 1 diabetes. Lancet 367(9513):847–858. https://doi.org/10.1016/s0140-6736(06)68341-4

    Article  CAS  PubMed  Google Scholar 

  11. Yoon J-W, Jun H-S (2005) Autoimmune destruction of pancreatic beta cells. Am J Ther 12(6):580–591. https://doi.org/10.1097/01.mjt.0000178767.67857.63

    Article  PubMed  Google Scholar 

  12. Lee SC, Pervaiz S (2007) Apoptosis in the pathophysiology of diabetes mellitus. Int J Biochem Cell Biol 39(3):497–504. https://doi.org/10.1016/j.biocel.2006.09.007

    Article  CAS  PubMed  Google Scholar 

  13. Nakano M, Matsumoto I, Sawada T, Ansite J, Oberbroeckling J, Zhang HJ, Kirchhof N, Shearer J, Sutherland DER, Hering BJ (2004) Caspase-3 inhibitor prevents apoptosis of human islets immediately after isolation and improves islet graft function. Pancreas 29(2):104–109. https://doi.org/10.1097/00006676-200408000-00004

    Article  CAS  PubMed  Google Scholar 

  14. Chandra J, Zhivotovsky B, Zaitsev S, Juntti-Berggren L, Berggren PO, Orrenius S (2001) Role of apoptosis in pancreatic beta-cell death in diabetes. Diabetes 50:S44–S47. https://doi.org/10.2337/diabetes.50.2007.S44

    Article  CAS  PubMed  Google Scholar 

  15. Gross A, McDonnell JM, Korsmeyer SJ (1999) BCL-2 family members and the mitochondria in apoptosis. Genes Dev 13(15):1899–1911. https://doi.org/10.1101/gad.13.15.1899

    Article  CAS  PubMed  Google Scholar 

  16. Montanya E, Tellez N (2009) Pancreatic remodeling: beta-cell apoptosis, proliferation and neogenesis, and the measurement of beta-cell mass and of individual beta-cell size. Method Mol Biol 560:137–158. https://doi.org/10.1007/978-1-59745-448-3_11

    Article  CAS  Google Scholar 

  17. Forouzanfar F, Goli AA, Asadpour E, Ghorbani A, Sadeghnia HR (2013) Protective effect of Punica granatum L. against serum/glucose deprivation-induced PC12 cells injury. Evid Based Complement Alternat Med. https://doi.org/10.1155/2013/716730

  18. Sharma V, Kalim S, Srivastava MK, Nanda S, Mishra S (2009) Oxidative stress and coxsackievirus infections as mediators of beta cell damage: a review. Sci Res Essays 4(2):42–58

    Google Scholar 

  19. Daisy P, Jasmine R, Ignacimuthu S, Murugan E (2009) A novel steroid from Elephantopus scaber L. an Ethnomedicinal plant with antidiabetic activity. Phytomedicine 16(2–3):252–257. https://doi.org/10.1016/j.phymed.2008.06.001

    Article  CAS  PubMed  Google Scholar 

  20. Pushparaj P, Tan CH, Tan BKH (2000) Effects of Averrhoa bilimbi leaf extract on blood glucose and lipids in streptozotocin-diabetic rats. J Ethnopharmacol 72(1–2):69–76. https://doi.org/10.1016/s0378-8741(00)00200-2

    Article  CAS  PubMed  Google Scholar 

  21. Dhanabal SP, Kokate CK, Ramanathan M, Kumar EP, Suresh B (2006) Hypoglycaemic activity of Pterocarpus marsupium Roxb. Phytother Res 20(1):4–8. https://doi.org/10.1002/ptr.1819

    Article  CAS  PubMed  Google Scholar 

  22. Schmidt RE, Dorsey DA, Beaudet LN, Plurad SB, Parvin CA, Miller MS (1999) Insulin-like growth factor I reverses experimental diabetic autonomic neuropathy. Am J Pathol 155(5):1651–1660. https://doi.org/10.1016/s0002-9440(10)65480-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pires DEV, Blundell TL, Ascher DB (2015) pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. J Med Chem 58(9):4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Morris GM, Lim-Wilby M (2008) Molecular docking. Method Mol Biol 443:365–382. https://doi.org/10.1007/978-1-59745-177-2_19

    Article  CAS  Google Scholar 

  25. Lu Y, Wang Y, Xu Z, Yan X, Luo X, Jiang H, Zhu W (2009) C-X center dot center dot center dot H contacts in biomolecular systems: how they contribute to protein-ligand binding affinity. J Phys Chem B 113(37):12615–12621. https://doi.org/10.1021/jp906352e

    Article  CAS  PubMed  Google Scholar 

  26. Wei MC, Zong WX, Cheng EHY, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacCregor GR, Thompson CB, Korsmeyer SJ (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292(5517):727–730. https://doi.org/10.1126/science.1059108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26(4):239–257. https://doi.org/10.1038/bjc.1972.33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Finegood DT, Scaglia L, Bonner-Weir S (1995) Dynamics of beta-cell mass in the growing rat pancreas. Estimation with a simple mathematical model. Diabetes 44(3):249–256. https://doi.org/10.2337/diabetes.44.3.249

    Article  CAS  PubMed  Google Scholar 

  29. Green DR (2005) Apoptotic pathways: ten minutes to dead. Cell 121(5):671–674. https://doi.org/10.1016/j.cell.2005.05.019

    Article  CAS  PubMed  Google Scholar 

  30. Qian S-B, Waldron L, Choudhary N, Klevit RE, Chazin WJ, Patterson C (2009) Engineering a ubiquitin ligase reveals conformational flexibility required for ubiquitin transfer. J Biol Chem 284(39):26797–26802. https://doi.org/10.1074/jbc.M109.032334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Biotechnology and Bioinformatics, Bishop Heber College, Tiruchirappalli, Tamilnadu, India

    R. Jasmine & A. Sherlin Rosita

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  1. R. Jasmine
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  2. A. Sherlin Rosita
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Editors and Affiliations

  1. School of Pharmaceutical Science and Technology, Tianjin University, Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Tianjin, China

    Haixia Chen

  2. State Key Laboratory of Food Nutrition and Safety, Tianjin Agricultural University, Tianjin, China

    Min Zhang

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Jasmine, R., Sherlin Rosita, A. (2021). Regeneration of Beta Cells by Inhibition of pro-Apoptotic Proteins through Phytocompound in STZ Induced Diabetic Albino Wistar Rats: In Vivo and In Silico Approach. In: Chen, H., Zhang, M. (eds) Structure and Health Effects of Natural Products on Diabetes Mellitus. Springer, Singapore. https://doi.org/10.1007/978-981-15-8791-7_12

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