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Swimming training attenuates pancreatic apoptosis through miR-34a/Sirtu in1/P53 Axis in high-fat diet and Streptozotocin-induced Type-2 diabetic rats

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Abstract

Objective

The present study sought to evaluate the miR-34a/Sirtuin1/p53 pro-apoptotic pathway, and reveal its modulation in diabetic rats undergoing swimming exercise.

Methods

Twenty-eight male Wistar rats were divided into four groups. They were inducted to develop diabetes by injection of streptozotocin. After 12 weeks of swimming, the pancreatic tissue of these rats were removed to be evaluated for the expression level of Sitruin1/P53/miR-34a through qPCR.

Results

Findings indicated a marked rise in the expression of miR-34 and P53 (P < 0.01) as well as a significant decrease in expression of Sitruin1 (P < 0.01) in the diabetic group. In contrast, swimming resulted in a significant decrease in miR-34a expression (P < 0.01), and a prominent rise in the level of Sitruin1 in the swimming-trained-diabetic group (P < 0.01). Additionally, high, moderate and low apoptosis rate were observed in the pancreatic tissue of the diabetic, swimming-trained diabetic, and control groups, respectively.

Conclusion

Our findings suggested a correlation between pancreatic tissue apoptosis rate and miR-34a/Sitruin1/p53 signaling, that was subject to modulation by training.

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References

  1. Association, A.D., 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2019. Diabetes Care, 2019. 42(Suppl 1): p. S13.

  2. Qi L, Liang J. Interactions between genetic factors that predict diabetes and dietary factors that ultimately impact on risk of diabetes. Curr Opin Lipidol. 2010;21(1):31–7.

    Article  CAS  Google Scholar 

  3. Saremi A, Shahrjerdi S, Kavyani A. The effect of aerobic training on metabolic parameters and serum level of Sirtuin1 in women with type 2 diabetes. AMUJ. 2016;19(114):88–97.

    Google Scholar 

  4. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444(7121):840–6.

    Article  CAS  Google Scholar 

  5. Chang Y-C, Chuang L-M. The role of oxidative stress in the pathogenesis of type 2 diabetes: from molecular mechanism to clinical implication. Am J Transl Res. 2010;2(3):316.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Tomita T. Apoptosis in pancreatic β-islet cells in type 2 diabetes. Bosnian journal of basic medical sciences. 2016;16(3):162–79.

    Article  CAS  Google Scholar 

  7. Norouzi M, Yasamineh S, Montazeri M, Dadashpour M, Sheervalilou R, Abasi M, et al. Recent advances on nanomaterials-based fluorimetric approaches for microRNAs detection. Mater Sci Eng C. 2019;104:110007.

  8. Sheervalilou R, Shirvaliloo S, Fekri Aval S, Khamaneh AM, Sharifi A, Ansarin K, et al. A new insight on reciprocal relationship between microRNA expression and epigenetic modifications in human lung cancer. Tumor Biol. 2017;39(5):1010428317695032.

  9. Sheervalilou R, Khamaneh AM, Sharifi A, Nazemiyeh M, Taghizadieh A, Ansarin K, et al. Using miR-10b, miR-1 and miR-30a expression profiles of bronchoalveolar lavage and sputum for early detection of non-small cell lung cancer. Biomed Pharmacother. 2017;88:1173–82.

  10. Guay C, Roggli E, Nesca V, Jacovetti C, Regazzi R. Diabetes mellitus, a microRNA-related disease? Transl Res. 2011;157(4):253–64.

    Article  CAS  Google Scholar 

  11. Improta Caria A, Nonaka C, Pereira C, Soares M, Macambira S, Souza B. Exercise training-induced changes in microRNAs: beneficial regulatory effects in hypertension, type 2 diabetes, and obesity. Int J Mol Sci. 2018;19(11):3608.

    Article  Google Scholar 

  12. Aval SF, Lotfi H, Sheervalilou R, Zarghami N. Tuning of major signaling networks (TGF-β, Wnt, notch and hedgehog) by miRNAs in human stem cells commitment to different lineages: possible clinical application. Biomed Pharmacother. 2017;91:849–60.

    Article  CAS  Google Scholar 

  13. Kafshdooz L, et al. The role of microRNAs and nanoparticles in ovarian cancer: a review. Artificial cells, nanomedicine, and biotechnology. 2018;46(sup2):241–7.

    Article  CAS  Google Scholar 

  14. Sheervalilou R, et al. Electrochemical Nano-biosensors as novel approach for the detection of lung Cancer-related MicroRNAs. Curr Mol Med. 2020;20(1):13–35.

    Article  CAS  Google Scholar 

  15. Sheervalilou R et al. (2019) CirculatingMiR-10b, MiR-1 and MiR-30a expression profiles in lung Cancer: possible correlation with Clinico-pathologic characteristics and lung Cancer detection. International Journal of Molecular and Cellular Medicine, 8(2): p. 0–0.

  16. Bahmanpour Z, Sheervalilou R, Choupani J, Shekari Khaniani M, Montazeri V, Mansoori Derakhshan S. A new insight on serum microRNA expression as novel biomarkers in breast cancer patients. J Cell Physiol. 2019;234:19199–211.

    Article  CAS  Google Scholar 

  17. Ortega FJ, Mercader JM, Moreno-Navarrete JM, Rovira O, Guerra E, Esteve E, et al. Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization. Diabetes Care. 2014;37(5):1375–83.

  18. Lin X, Guan H, Huang Z, Liu J, Li H, Wei G, et al. Downregulation of Bcl-2 expression by miR-34a mediates palmitate-induced Min6 cells apoptosis. Journal of diabetes research. 2014;2014:17.

  19. Yamakuchi M, Ferlito M, Lowenstein CJ. miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci. 2008;105(36):13421–6.

    Article  CAS  Google Scholar 

  20. Lee J, Kemper JK. Controlling SIRT1 expression by microRNAs in health and metabolic disease. Aging. 2010;2(8):527–34.

    Article  CAS  Google Scholar 

  21. Chang T-C, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007;26(5):745–52.

  22. Panasiuk A, et al. Expression of p53, Bax and Bcl-2 proteins in hepatocytes in non-alcoholic fatty liver disease. World J Gastroenterol: WJG. 2006;12(38):6198.

    Article  CAS  Google Scholar 

  23. Yu J et al. (2016) Exercise improved lipid metabolism and insulin sensitivity in rats fed a high-fat diet by regulating glucose transporter 4 (GLUT4) and musclin expression. Braz J Med Biol Res, 49(5)

  24. Ghiasi R et al. (2019) Swimming training by affecting the pancreatic Sirtuin1 (SIRT1) and oxidative stress, improves insulin sensitivity in diabetic male rats. Horm Mol Biol Clin Invest, 40(3)

  25. Sigal RJ, Kenny GP, Wasserman DH, Castaneda-Sceppa C. Physical activity/exercise and type 2 diabetes. Diabetes Care. 2004;27(10):2518–39.

    Article  Google Scholar 

  26. Habibi F, Ghadiri Soufi F, Ghiasi R, Khamaneh AM, Alipour MR. Alteration in inflammation-related miR-146a expression in NF-KB signaling pathway in diabetic rat hippocampus. Advanced pharmaceutical bulletin. 2016;6(1):99–103.

    Article  CAS  Google Scholar 

  27. Pezhman L et al. (2018) The impact of forced swimming on expression of RANKL and OPG in a type 2 diabetes mellitus rat model. Arch Physiol Biochem, p. 1–6

  28. Carrillo M-C, Kanai S, Nokubo M, Kitani K. (−) Deprenyl induces activities of both superoxide dismutase and catalase but not of glutathione peroxidase in the striatum of young male rats. Life Sci. 1991;48(6):517–21.

    Article  CAS  Google Scholar 

  29. Hanke J. Apoptosis in cultured rat islets of langerhans and occurrence of Bcl-2, Bak, Bax, Fas and Fas ligand. Cells Tissues Organs. 2001;169(2):113–24.

    Article  CAS  Google Scholar 

  30. Orimo M, Minamino T, Miyauchi H, Tateno K, Okada S, Moriya J, et al. Protective role of SIRT1 in diabetic vascular dysfunction. Arteriosclerosis, thrombosis, vascular biology. 2009;29(6):889–94.

  31. Jiang L, Zhang X, Zheng X, Ru A, Ni X, Wu Y, et al. Apoptosis, senescence, and autophagy in rat nucleus pulposus cells: implications for diabetic intervertebral disc degeneration. J Orthop Res. 2013;31(5):692–702.

  32. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107(9):1058–70.

    Article  CAS  Google Scholar 

  33. Chen D, Xia D, Pan Z, Xu D, Zhou Y, Wu Y, et al. Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo. Cell Death Disease. 2016;7(10):e2441–1.

  34. Lupi R, Dotta F, Marselli L, del Guerra S, Masini M, Santangelo C, et al. Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that β-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated. Diabetes. 2002;51(5):1437–42.

  35. Cnop M, Welsh N, Jonas JC, Jorns A, Lenzen S, Eizirik DL. Mechanisms of pancreatic β-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes. 2005;54(suppl 2):S97–S107.

    Article  CAS  Google Scholar 

  36. Federici M, Hribal M, Perego L, Ranalli M, Caradonna Z, Perego C, et al. High glucose causes apoptosis in cultured human pancreatic islets of Langerhans: a potential role for regulation of specific Bcl family genes toward an apoptotic cell death program. Diabetes. 2001;50(6):1290–301.

  37. Lovis P, Roggli E, Laybutt DR, Gattesco S, Yang JY, Widmann C, et al. Alterations in microRNA expression contribute to fatty acid–induced pancreatic β-cell dysfunction. Diabetes. 2008;57(10):2728–36.

  38. Li S, Chen X, Zhang H, Liang X, Xiang Y, Yu C, et al. Differential expression of microRNAs in mouse liver under aberrant energy metabolic status. J Lipid Res. 2009;50(9):1756–65.

  39. Kong L, Zhu J, Han W, Jiang X, Xu M, Zhao Y, et al. Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study. Acta Diabetol. 2011;48(1):61–9.

  40. Ji Q, Hao X, Zhang M, Tang W, Yang M, Li L, et al. MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS One. 2009;4(8):e6816.

  41. Backe MB, Novotny GW, Christensen DP, Grunnet LG, Mandrup-Poulsen T. Altering β-cell number through stable alteration of miR-21 and miR-34a expression. Islets. 2014;6(1):e27754.

    Article  Google Scholar 

  42. Roggli E, Britan A, Gattesco S, Lin-Marq N, Abderrahmani A, Meda P, et al. Involvement of microRNAs in the cytotoxic effects exerted by proinflammatory cytokines on pancreatic β-cells. Diabetes. 2010;59(4):978–86.

  43. Strycharz J, Rygielska Z, Swiderska E, Drzewoski J, Szemraj J, Szmigiero L, et al. SIRT1 as a therapeutic target in diabetic complications. Curr Med Chem. 2018;25(9):1002–35.

  44. Shi X, Pi L, Zhou S, Li X, Min F, Wang S, et al. Activation of sirtuin 1 attenuates high glucose-induced neuronal apoptosis by deacetylating p53. Front Endocrinol. 2018;9:274.

  45. Jiao D, Zhang H, Jiang Z, Huang W, Liu Z, Wang Z, et al. MicroRNA-34a targets sirtuin 1 and leads to diabetes-induced testicular apoptotic cell death. J Mol Med. 2018;96(9):939–49.

  46. Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X, et al. SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab. 2007;6(4):307–19.

  47. Liang F, Kume S, Koya D. SIRT1 and insulin resistance. Nat Rev Endocrinol. 2009;5(7):367–73.

    Article  CAS  Google Scholar 

  48. Teixeira-Lemos E, Nunes S, Teixeira F, Reis F. Regular physical exercise training assists in preventing type 2 diabetes development: focus on its antioxidant and anti-inflammatory properties. Cardiovasc Diabetol. 2011;10(1):12.

    Article  Google Scholar 

  49. Quindry J, et al. Exercise training provides cardioprotection against ischemia–reperfusion induced apoptosis in young and old animals. Exp Gerontol. 2005;40(5):416–25.

    Article  CAS  Google Scholar 

  50. Chen Z-P, Stephens TJ, Murthy S, Canny BJ, Hargreaves M, Witters LA, et al. Effect of exercise intensity on skeletal muscle AMPK signaling in humans. Diabetes. 2003;52(9):2205–12.

  51. Zhang C, Feng Y, Qu S, Wei X, Zhu H, Luo Q, et al. Resveratrol attenuates doxorubicin-induced cardiomyocyte apoptosis in mice through SIRT1-mediated deacetylation of p53. Cardiovasc Res. 2011;90(3):538–45.

  52. Huang C-C, Wang T, Tung YT, Lin WT. Effect of exercise training on skeletal muscle SIRT1 and PGC-1α expression levels in rats of different age. Int J Med Sci. 2016;13(4):260–70.

    Article  CAS  Google Scholar 

  53. Casuso RA, Martínez-Amat A, Hita-Contreras F, Camiletti-Moirón D, Aranda P, Martínez-López E. Quercetin supplementation does not enhance cerebellar mitochondrial biogenesis and oxidative status in exercised rats. Nutr Res. 2015;35(7):585–91.

    Article  CAS  Google Scholar 

  54. Marton O, Koltai E, Takeda M, Koch LG, Britton SL, Davies KJA, et al. Mitochondrial biogenesis-associated factors underlie the magnitude of response to aerobic endurance training in rats. Pflügers Archiv-European Journal of Physiology. 2015;467(4):779–88.

  55. Improta Caria AC, et al. Exercise training-induced changes in MicroRNAs: beneficial regulatory effects in hypertension, type 2 diabetes, and obesity. Int J Mol Sci. 2018;19(11):3608.

    Article  Google Scholar 

  56. Da JSN, et al. Swimming training in rats increases cardiac MicroRNA-126 expression and angiogenesis. Med Sci Sports Exerc. 2012;44(8):1453–62.

    Article  Google Scholar 

  57. Fernandes T, Magalhães FC, Roque FR, Phillips MI, Oliveira EM. Exercise training prevents the microvascular rarefaction in hypertension balancing angiogenic and apoptotic factors: role of microRNAs-16,-21, and-126. Hypertension. 2012;59(2):513–20.

    Article  CAS  Google Scholar 

  58. Kou X, Li J, Liu X, Chang J, Zhao Q, Jia S, et al. Swimming attenuates d-galactose-induced brain aging via suppressing miR-34a-mediated autophagy impairment and abnormal mitochondrial dynamics. J Appl Physiol. 2017;122(6):1462–9.

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Acknowledgments

This study was endorsed by Liver and Gastrointestinal Diseases Research Center of Tabriz University of Medical Sciences (project No: 5/4/610). Special thanks for Milad Shirvaliloo editing job on the manuscript.

Funding

This study was funded by Liver and Gastrointestinal Diseases Research Center of Tabriz University of Medical Sciences (project No: 5/4/610).

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Authors and Affiliations

Authors

Contributions

Mohammad Reza Alipour and Rafighe Ghiasi designed the project. Rafighe Ghiasi, Roya Naderi and Alireza Alihemmati performed the required tests. Rafighe Ghiasi and Roghayeh Sheervalilou performed statistical analysis, and prepared the manuscript draft and revised it.

Corresponding author

Correspondence to Rafighe Ghiasi.

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The authors have affirmed that there is no conflict of interest.

Ethical issues

The protocol for this study was planned to follow the guidelines of NIH, and be in agreement with Ethics Committee for the Use of Animals in Research at Tabriz University of Medical Sciences (project No: 5/4/610).

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Alipour, M.R., Naderi, R., Alihemmati, A. et al. Swimming training attenuates pancreatic apoptosis through miR-34a/Sirtu in1/P53 Axis in high-fat diet and Streptozotocin-induced Type-2 diabetic rats. J Diabetes Metab Disord 19, 1439–1446 (2020). https://doi.org/10.1007/s40200-020-00670-6

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  • DOI: https://doi.org/10.1007/s40200-020-00670-6

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