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Changes in Titin and Collagen Modulate Effects of Aerobic and Resistance Exercise on Diabetic Cardiac Function

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Abstract

Diastolic dysfunction is a common complication that occurs early in diabetes mellitus. Titin and collagen are two important regulators of myocardial passive tension, which contributes to diabetic myocardial diastolic dysfunction. Exercise therapy significantly improves the impaired diabetic cardiac function, but its benefits appear to depend on the type of exercise used. We investigated the effect of aerobic and resistance exercise on cardiac diastolic function in diabetic rats induced by high-fat diet combined with low-dose streptozotocin injection. Interestingly, although resistance training had a more pronounced effect on blood glucose control than did aerobic training in type 2 diabetic rats, improvements in cardiac diastolic parameters benefited more from aerobic training. Moreover, aerobic exercise did significantly increase the expression levels of titin and decrease collagen I, TGFβ1 expression level. In summary, out data suggest that aerobic exercise may improve diabetic cardiac function through changes in titin-dependent myocardial stiffness rather than collagen-dependent interstitial fibrosis.

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References

  1. Zile, M. R., Baicu, C. F., Ikonomidis, J. S., Stroud, R. E., Nietert, P. J., Bradshaw, A. D., Slater, R., Palmer, B. M., Van Buren, P., Meyer, M., Redfield, M. M., Bull, D. A., Granzier, H. L., & LeWinter, M. M. (2015). Myocardial stiffness in patients with heart failure and a preserved ejection fraction: contributions of collagen and titin. Circulation., 131, 1247–1259. https://doi.org/10.1161/CIRCULATIONAHA.114.013215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. LeWinter, M. M., & Granzier, H. L. (2014). Cardiac titin and heart disease. Journal of Cardiovascular Pharmacology, 63, 207–212. https://doi.org/10.1097/FJC.0000000000000007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ricard-Blum, S. (2016). The collagen family. Cold Spring Harbor Perspectives in Biology, 3, a004978. https://doi.org/10.1101/cshperspect.a004978.

    Article  Google Scholar 

  4. Franssen, C., & González Miqueo, A. (2016). The role of titin and extracellular matrix remodelling in heart failure with preserved ejection fraction. Netherlands Heart Journal, 24, 259–267. https://doi.org/10.1007/s12471-016-0812-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Granzier, H. L., & Irving, T. C. (1995). Passive tension in cardiac muscle: contribution of collagen, titin, microtubules, and intermediate filaments. Biophysical Journal, 68, 1027–1044. https://doi.org/10.1016/S0006-3495(95)80278-X.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Goyal, B., & Mehta, A. (2013). Diabetic cardiomyopathy: pathophysiological mechanisms and cardiac dysfuntion. Human & Experimental Toxicology, 32, 571–590. https://doi.org/10.1177/0960327112450885.

    Article  CAS  Google Scholar 

  7. Hölscher, M., Bode, C., & Bugger, H. (2016). Diabetic cardiomyopathy: does the type of diabetes matter? International Journal of Molecular Sciences, 17, 2136. https://doi.org/10.3390/ijms17122136.

    Article  PubMed Central  Google Scholar 

  8. Schannwell, C. M., Schneppenheim, M., Perings, S., Plehn, G., & Strauer, B. E. (2002). Left ventricular diastolic dysfunction as an early manifestation of diabetic cardiomyopathy. Cardiology., 98, 33–39. https://doi.org/10.1159/000064682.

    Article  CAS  PubMed  Google Scholar 

  9. Yilmaz, S., Canpolat, U., Aydogdu, S., & Abboud, H. E. (2015). Diabetic cardiomyopathy; summary of 41 years. Korean Circulation Journal, 45, 266–272. https://doi.org/10.4070/kcj.2015.45.4.266.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Brunvand, L., Fugelseth, D., Stensaeth, K. H., Dahl-Jørgensen, K., & Margeirsdottir, H. D. (2016). Early reduced myocardial diastolic function in children and adolescents with type 1 diabetes mellitus a population-based study. BMC Cardiovascular Disorders, 16, 103. https://doi.org/10.1186/s12872-016-0288-1.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Hamdani, N., Franssen, C., Lourenço, A., Falcão-Pires, I., Fontoura, D., Leite, S., Plettig, L., López, B., Ottenheijm, C. A., Becher, P., González, A., Tschöpe, C., Díez, J., Linke, W., Leite Moreira, A., & Paulus, W. (2013). Myocardial titin hypophosphorylation importantly contributes to heart failure with preserved ejection fraction in a rat metabolic risk model. Circulation. Heart Failure, 6, 1239–1249. https://doi.org/10.1161/CIRCULATIONAHA.114.013215.

    Article  CAS  PubMed  Google Scholar 

  12. Krüger, M., Babicz, K., von Frieling-Salewsky, M., & Linke, W. A. (2010). Insulin signaling regulates cardiac titin properties in heart development and diabetic cardiomyopathy. Journal of Molecular and Cellular Cardiology, 48, 910–916. https://doi.org/10.1016/j.yjmcc.2010.02.012.

    Article  CAS  PubMed  Google Scholar 

  13. Tokudome, T., Horio, T., Yoshihara, F., Suga, S.-i., Kawano, Y., Kohno, M., & Kangawa, K. (2004). Direct effects of high glucose and insulin on protein synthesis in cultured cardiac myocytes and DNA and collagen synthesis in cardiac fibroblasts. Metabolism., 53, 710–715. https://doi.org/10.1016/j.metabol.2004.01.006.

    Article  CAS  PubMed  Google Scholar 

  14. Souders, C. A., Bowers, S. L. K., & Baudino, T. A. (2009). Cardiac fibroblast: the renaissance cell. Circulation Research, 105, 1164–1176. https://doi.org/10.1161/CIRCRESAHA.109.209809.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bacchi, E., Negri, C., Zanolin, M. E., Milanese, C., Faccioli, N., Trombetta, M., Zoppini, G., Cevese, A., Bonadonna, R. C., Schena, F., Bonora, E., Lanza, M., & Moghetti, P. (2012). Metabolic effects of aerobic training and resistance training in type 2 diabetic subjects: a randomized controlled trial (the RAED2 study). Diabetes Care, 35, 676–682. https://doi.org/10.2337/dc11-1655.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hidalgo, C., Saripalli, C., & Granzier, H. L. (2014). Effect of exercise training on post-translational and post-transcriptional regulation of titin stiffness in striated muscle of wild type and IG KO mice. Archives of Biochemistry and Biophysics, 552–553, 100–107. https://doi.org/10.2337/dc11-1655.

    Article  CAS  PubMed  Google Scholar 

  17. Hayashi, T., Wojtaszewski, F. P., & Goodyear, L. J. (1997). Execise regulation of glucose transport in skeletal muscle. American Journal of Physiology. Endocrinology and Metabolism, 273, E1039–E1051. https://doi.org/10.1152/ajpendo.1997.273.6.E1039.

    Article  CAS  Google Scholar 

  18. Ribeiro, C., Cambri, L. T., Dalia, R. A., de Araújo, M. B., Botezelli, J. D., Sponton, A. C. S., & de Mello, M. A. R. (2012). Effects of physical training with different intensities of effort on lipid metabolism in rats submitted to the neonatal application of alloxan. Lipids in Health and Disease, 11, 138. https://doi.org/10.1186/1476-511X-11-138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sylow, L., Kleinert, M., Richter, E., & Jensen, T. (2017). Exercise-stimulated glucose uptake — regulation and implications for glycaemic control. Nature Reviews. Endocrinology, 13, 133–148. https://doi.org/10.1038/nrendo.2016.162.

    Article  CAS  PubMed  Google Scholar 

  20. Cauza, E., Hanusch-Enserer, U., Strasser, B., Ludvik, B., Metz-Schimmerl, S., Pacini, G., Wagner, O., Georg, P., Prager, R., Kostner, K., Dunky, A., & Haber, P. (2005). The relative benefits of endurance and strength training on the metabolic factors and muscle function of people with type 2 diabetes mellitus. Archives of Physical Medicine and Rehabilitation, 86, 1527–1533. https://doi.org/10.1016/j.apmr.2005.01.007.

    Article  PubMed  Google Scholar 

  21. Ishiguro, H., Kodama, S., Horikawa, C., Fujihara, K., Sugawara Hirose, A., Hirasawa, R., Yachi, Y., Ohara, N., Shimano, H., Hanyu, O., & Sone, H. (2015). Search of the ideal resistance training program to improve glycemic control and its indication for patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Sports Medicine, 46, 67–77. https://doi.org/10.1007/s40279-015-0379-7.

    Article  Google Scholar 

  22. Ivy, J. (1997). Role of exercise training in the prevention and treatment of insulin resistance and non-insulin-dependent diabetes mellitus. Sports Medicine, 24, 321–336. https://doi.org/10.2165/00007256-199724050-00004.

    Article  CAS  PubMed  Google Scholar 

  23. Weeks, D. L. (2007). Exercise interventions for diabetes control: do we really know that strength training is better than endurance training? Archives of Physical Medicine and Rehabilitation, 88, 397. https://doi.org/10.1016/j.apmr.2007.01.008.

    Article  PubMed  Google Scholar 

  24. Stalin, A., Irudayaraj, S. S., Gandhi, G. R., Balakrishna, K., Ignacimuthu, S., & Al-Dhabi, N. A. (2016). Hypoglycemic activity of 6-bromoembelin and vilangin in high-fat diet fed-streptozotocin-induced type 2 diabetic rats and molecular docking studies. Life Sciences, 153, 100–117. https://doi.org/10.1016/j.lfs.2016.04.016.

    Article  CAS  PubMed  Google Scholar 

  25. Epp, R. A., Susser, S. E., Morissette, M. P., Kehler, D. S., Jassal, D. S., & Duhamel, T. A. (2012). Exercise training prevents the development of cardiac dysfunction in the low-dose streptozotocin diabetic rats fed a high-fat diet. Canadian Journal of Physiology and Pharmacology, 91, 80–89. https://doi.org/10.1139/cjpp-2012-0294.

    Article  CAS  PubMed  Google Scholar 

  26. Gu, H., Xia, X., Chen, Z., Liang, H., Yan, J., Xu, F., & Weng, J. (2014). Insulin therapy improves islet functions by restoring pancreatic vasculature in high-fat diet-fed streptozotocin-diabetic rats. Journal of Diabetes, 6, 228–236. https://doi.org/10.1111/1753-0407.12095.

    Article  CAS  PubMed  Google Scholar 

  27. Bedford, T. G., Tipton, C. M., Wilson, N. C., Oppliger, R. A., & Gisolfi, C. V. (1979). Maximum oxygen consumption of rats and its changes with various experimental procedures. Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology, 47, 1278–1283. https://doi.org/10.1152/jappl.1979.47.6.1278.

    Article  CAS  Google Scholar 

  28. Hornberger, T. A., Jr., & Farrar, R. P. (2004). Physiological hypertrophy of the FHL muscle following 8 weeks of progressive resistance exercise in the rat. Canadian Journal of Applied Physiology, 29, 16–31. https://doi.org/10.1139/h04-002.

    Article  CAS  PubMed  Google Scholar 

  29. Fang, Z. Y., Prins, J. B., & Marwick, T. H. (2004). Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. Endocrine Reviews, 25, 543–567. https://doi.org/10.1210/er.2003-0012.

    Article  CAS  PubMed  Google Scholar 

  30. Jia, G., Whaley-Connell, A., & Sowers, J. R. (2018). Diabetic cardiomyopathy: a hyperglycaemia- and insulin-resistance-induced heart disease. Diabetologia., 61, 21–28. https://doi.org/10.1007/s00125-017-4390-4.

    Article  CAS  PubMed  Google Scholar 

  31. Astorri, E., Fiorina, P., Astorri, A., Contini, G. A., Albertini, D., Magnati, G., & Lanfredini, M. (1997). Isolated and preclinical impairment of left ventricular filling in insulin-dependent and non-insulin-dependent diabetic patients. Clinical Cardiology, 20, 536–540. https://doi.org/10.1002/clc.4960200606.

    Article  CAS  PubMed  Google Scholar 

  32. Aziz, F., Tk, L.-A., Enweluzo, C., Dutta, S., & Zaeem, M. (2013). Diastolic heart failure: a concise review. Journal of Clinical Medical Research, 5, 327–334. https://doi.org/10.4021/jocmr1532w.

    Article  Google Scholar 

  33. Boyer, J. K., Thanigaraj, S., Schechtman, K. B., & Pérez, J. E. (2004). Prevalence of ventricular diastolic dysfunction in asymptomatic, normotensive patients with diabetes mellitus. The American Journal of Cardiology, 93, 870–875. https://doi.org/10.1016/j.amjcard.2003.12.026.

    Article  PubMed  Google Scholar 

  34. Böhm, A., Weigert, C., Staiger, H., & Häring, H.-U. (2016). Exercise and diabetes: relevance and causes for response variability. Endocrine., 51, 390–401. https://doi.org/10.1007/s12020-015-0792-6.

    Article  PubMed  Google Scholar 

  35. Rees, J. L., Johnson, S. T., & Boulé, N. (2017). Aquatic exercise for adults with type 2 diabetes: a meta-analysis. Acta Diabetologica, 54, 895–904. https://doi.org/10.1007/s00592-017-1023-9.

    Article  PubMed  Google Scholar 

  36. Ried-Larsen, M., MacDonald, C. S., Johansen, M. Y., Hansen, K., Christensen, R., Almdal, T. P., Pedersen, B. K., & Karstoft, K. (2018). Why prescribe exercise as therapy in type 2 diabetes? We have a pill for that! Diabetes/Metabolism Research and Reviews, 34, e2999. https://doi.org/10.1002/dmrr.2999.

    Article  PubMed  Google Scholar 

  37. Solene Le Douairon, L., Francoise Rannou, B., & Tom, B. (2014). Physical activity and diabetic cardiomyopathy: myocardial adaptation depending on exercise load. Current Diabetes Reviews, 10, 371–390. https://doi.org/10.2174/1573399811666141229151421.

    Article  Google Scholar 

  38. Brown, B., Somauroo, J., Green, D., Wilson, M., Drezner, J., George, K., & Oxborough, D. (2017). The complex phenotype of the athlete’s heart: implications for preparticipation screening. Exercise and Sport Sciences Reviews, 45, 96–104. https://doi.org/10.1249/JES.0000000000000102.

    Article  PubMed  Google Scholar 

  39. Morganroth, J., Maron, B. J., Henry, W. L., & Epstein, S. E. (1975). Comparative left ventricular dimensions in trained athletes. Annals of Internal Medicine, 82, 521–524. https://doi.org/10.7326/0003-4819-82-4-521.

    Article  CAS  PubMed  Google Scholar 

  40. Eliane Hopf, A., Andresen, C., Kötter, S., Isic, M., Ulrich, K., Salcan, S., Bongardt, S., Roell, W., Drove, F., Scheerer, N., Vandekerckhove, L., Keulenaer, G., Hamdani, N., Linke, W., & Krüger, M. (2018). Diabetes-induced cardiomyocyte passive stiffening is caused by impaired insulin-dependent titin modification and can be modulated by neuregulin-1. Circulation Research, 123, 342–355. https://doi.org/10.1161/CIRCRESAHA.117.312166}.

    Article  CAS  Google Scholar 

  41. Røe, Å. T., Aronsen, J. M., Skårdal, K., Hamdani, N., Linke, W. A., Danielsen, H. E., Sejersted, O. M., Sjaastad, I., & Louch, W. E. (2017). Increased passive stiffness promotes diastolic dysfunction despite improved Ca2+ handling during left ventricular concentric hypertrophy. Cardiovascular Research, 113, 1161–1172. https://doi.org/10.1093/cvr/cvx087.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Krüger, M., Kötter, S., Grützner, A., Lang, P., Andresen, C., Redfield, M. M., Butt, E., dos Remedios, C. G., & Linke, W. A. (2009). Protein kinase G modulates human myocardial passive stiffness by phosphorylation of the titin springs. Circulation Research, 104, 87–94. https://doi.org/10.1016/j.bpj.2008.12.2003.

    Article  PubMed  Google Scholar 

  43. Nagueh, S. F., Shah, G., Wu, Y., Torre-Amione, G., King, N. M. P., Lahmers, S., Witt, C. C., Becker, K., Labeit, S., & Granzier, H. L. (2004). Altered titin expression, myocardial stiffness, and left ventricular function in patients with dilated cardiomyopathy. Circulation., 110, 155–162. https://doi.org/10.1161/01.CIR.0000135591.37759.AF.

    Article  CAS  PubMed  Google Scholar 

  44. Warren, C. M., Jordan, M. C., Roos, K. P., Krzesinski, P. R., & Greaser, M. L. (2003). Titin isoform expression in normal and hypertensive myocardium. Cardiovascular Research, 59, 86–94. https://doi.org/10.1016/S0008-6363(03)00328-6.

    Article  CAS  PubMed  Google Scholar 

  45. Wu, Y., Bell, S. P., Trombitas, K., Witt, C. C., Labeit, S., LeWinter, M. M., & Granzier, H. (2002). Changes in titin isoform expression in pacing-induced cardiac failure give rise to increased passive muscle stiffness. Circulation., 106, 1384–1389. https://doi.org/10.1161/01.CIR.0000029804.61510.02.

    Article  CAS  PubMed  Google Scholar 

  46. Yamasaki, R., Wu, Y., McNabb, M., Greaser, M., Labeit, S., & Granzier, H. (2002). Protein kinase A phosphorylates titin’s cardiac-specific N2B domain and reduces passive tension in rat cardiac myocytes. Circulation Research, 90, 1181–1188. https://doi.org/10.1161/01.RES.0000021115.24712.99.

    Article  CAS  PubMed  Google Scholar 

  47. Neagoe, C., Kulke, M., del Monte, F., Gwathmey, J. K., de Tombe, P. P., Hajjar, R. J., & Linke, W. A. (2002). Titin isoform switch in ischemic human heart disease. Circulation., 106, 1333–1341. https://doi.org/10.1161/01.CIR.0000029803.93022.93.

    Article  PubMed  Google Scholar 

  48. Hsu, K. L., Tsai, C. H., Chiang, F.-T., Lo, H., Tseng, C. D., Wang, S. M., Chen, C. F., & Tseng, Y. Z. (1997). Myocardial mechanics and titin in experimental insulin-resistant rats. Japanese Heart Journal, 38, 717–728. https://doi.org/10.1536/ihj.38.717.

    Article  CAS  PubMed  Google Scholar 

  49. Lehti, M., Silvennoinen, M., Kivelä, R., Kainulainen, H., & Komulainen, J. (2006). Effects of streptozotocin-induced diabetes and physical training on gene expression of extracellular matrix proteins in mouse skeletal muscle. American Journal of Physiology. Endocrinology and Metabolism, 290, E900–E9E7. https://doi.org/10.1152/ajpendo.00444.2005.

    Article  CAS  PubMed  Google Scholar 

  50. Shah, M. S., & Brownlee, M. (2016). Molecular and cellular mechanisms of cardiovascular disorders in diabetes. Circulation Research, 118, 1808–1829. https://doi.org/10.1161/CIRCRESAHA.116.306923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Teran-Garcia, M., Rankinen, T., Koza, R. A., Rao, D. C., & Bouchard, C. (2005). Endurance training-induced changes in insulin sensitivity and gene expression. American Journal of Physiology. Endocrinology and Metabolism, 288, 1168–1178. https://doi.org/10.1152/ajpendo.00467.2004.

    Article  Google Scholar 

  52. Mcguigan, M. R., Sharman, M. J., Newton, R. U., Davie, A. J., Murphy, A. J., & Mcbride, J. M. (2003). Effect of explosive resistance training on titin and myosin heavy chain isoforms in trained subjects. Journal of Strength and Conditioning Research, 17, 645–651. https://doi.org/10.1519/00124278-200311000-00004.

    Article  PubMed  Google Scholar 

  53. Kwak, H. B. (2013). Aging, exercise, and extracellular matrix in the heart. Journal of Exercise Rehabilitation., 9, 338–347. https://doi.org/10.12965/jer.130049.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Russo, I., & Frangogiannis, N. G. (2016). Diabetes-associated cardiac fibrosis: cellular effectors, molecular mechanisms and therapeutic opportunities. Journal of Molecular and Cellular Cardiology, 90, 84–93. https://doi.org/10.1016/j.yjmcc.2015.12.011.

    Article  CAS  PubMed  Google Scholar 

  55. Calligaris, S. D., Lecanda, M., Solis, F., Ezquer, M., Gutiérrez, J., Brandan, E., Leiva, A., Sobrevia, L., & Conget, P. (2013). Mice long-term high-fat diet feeding recapitulates human cardiovascular alterations: an animal model to study the early phases of diabetic cardiomyopathy. PLoS One, 8, e60931. https://doi.org/10.1371/journal.pone.0060931.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Namba, T., Tsutsui, H., Tagawa, H., Takahashi, M., & Takeshita, A. (1997). Regulation of fibrillar collagen gene expression and protein accumulation in volume-overloaded cardiac hypertrophy. Circulation, 95, 2448–2454. https://doi.org/10.1161/01.CIR.95.10.2448.

    Article  CAS  PubMed  Google Scholar 

  57. Norambuena-Soto, I., Núñez-Soto, C., Sanhueza Olivares, F., Cancino-Arenas, N., Mondaca-Ruff, D., Vivar, R., Diaz-Araya, G., Mellado, R., & Chiong, M. (2017). Transforming growth factor-beta and Forkhead box O transcription factors as cardiac fibroblast regulators. Bioscience Trends, 11, 154–162. https://doi.org/10.5582/bst.2017.01017.

    Article  CAS  PubMed  Google Scholar 

  58. Serralheiro, P., Cairrao, E., Maia, C. J., Joao, M., Almeida, C. M. C., & Verde, I. (2017). Effect of TGF-beta1 on MMP/TIMP and TGF-beta1 receptors in great saphenous veins and its significance on chronic venous insufficiency. Phlebology., 32, 334–341. https://doi.org/10.1177/0268355516655067.

    Article  PubMed  Google Scholar 

  59. Xu, H., He, Y., Feng, J. Q., Shu, R., Liu, Z., Li, J., Wang, Y., Xu, Y., Zeng, H., Xu, X., Xiang, Z., Xue, C., Bai, D., & Han, X. (2017). Wnt3α and transforming growth factor-β induce myofibroblast differentiation from periodontal ligament cells via different pathways. Experimental Cell Research, 353, 55–62. https://doi.org/10.1016/j.yexcr.2016.12.026.

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was funded by Sichuan Science and Technology Program [grant numbers 2018JY0499] and Sports Medicine key Laboratory of General Administration of Sport of China [grant numbers 2018-A008].

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Authors and Affiliations

  1. Institute of Sports Medicine and Health, Chengdu Sport Institute, Chengdu, 610041, China

    Shunchang Li, Min Liang & Derun Gao

  2. School of Sports Medicine and Health, Chengdu Sport Institute, Chengdu, 610041, China

    Quansheng Su

  3. Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada

    Ismail Laher

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  1. Shunchang Li
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Li, S., Liang, M., Gao, D. et al. Changes in Titin and Collagen Modulate Effects of Aerobic and Resistance Exercise on Diabetic Cardiac Function. J. of Cardiovasc. Trans. Res. 12, 404–414 (2019). https://doi.org/10.1007/s12265-019-09875-4

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