Skip to main content

Advertisement

SpringerLink
Log in

NOD Mice Recapitulate the Cardiac Disturbances Observed in Type 1 Diabetes

  • Original Article
  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

This work aimed at testing the hypothesis that NOD/ShiLtJ mice (NOD) recapitulate the cardiac disturbances observed on type 1 diabetes (T1D). NOD mice were studied 4 weeks after the onset of hyperglycemia, and NOR/Lt mice matched as control. Cardiac function was evaluated by echocardiography and electrocardiography (ECG). Action potentials (AP) and Ca2+ transients were evaluated at whole heart level. Heart mitochondrial function was evaluated by high-resolution respirometry and H2O2 release. NOD mice presented a reduction in hearth weight. Mitochondrial oxygen fluxes and H2O2 release were similar between NOD and NOR mice. ECG revealed a QJ interval prolongation in NOD mice. Furthermore, AP duration at 30% of repolarization was increased, and it depicted slower Ca2+ transient kinetics. NOD mice presented greater number/severity of ventricular arrhythmias both in vivo and in vitro. In conclusion, NOD mice evoked cardiac electrical and calcium handling disturbances similar to the observed in T1D.

.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Bullard, K. M., Cowie, C. C., Lessem, S. E., et al. (2018). Prevalence of diagnosed diabetes in adults by diabetes type — United States, 2016. Morbidity and Mortality Weekly Report, 67, 359–361.

    Article  Google Scholar 

  2. American Diabetes Association. (2014). Diagnosis and classification of diabetes mellitus. Diabetes Care, 37(Suppl 1), S81–S90. https://doi.org/10.2337/dc14-S081.

    Article  Google Scholar 

  3. Dabelea, D., Mayer-Davis, E. J., Saydah, S., et al. (2014). Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009. JAMA, 311, 1778. https://doi.org/10.1001/jama.2014.3201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Skyler, J. S., Bakris, G. L., Bonifacio, E., et al. (2017). Differentiation of diabetes by pathophysiology, natural history, and prognosis. Diabetes, 66, 241–255. https://doi.org/10.2337/db16-0806.

    Article  CAS  PubMed  Google Scholar 

  5. Stenström, G., Gottsäter, A., Bakhtadze, E., et al. (2005). Latent autoimmune diabetes in adults: Definition, prevalence, beta-cell function, and treatment. Diabetes, 54(Suppl 2), S68–S72. https://doi.org/10.2337/DIABETES.54.SUPPL_2.S68.

    Article  PubMed  Google Scholar 

  6. American Diabetes Association. (2019). 10. Cardiovascular disease and risk management: Standards of medical care in diabetes—2019. Diabetes Care, 42, S103–S123. https://doi.org/10.2337/dc19-s010.

    Article  CAS  Google Scholar 

  7. American Diabetes Association. (2019). 11. Microvascular complications and foot care: Standards of medical care in diabetesd2019. Diabetes Care, 42, S124–S138. https://doi.org/10.2337/dc19-s011.

    Article  CAS  Google Scholar 

  8. Rubler, S., Dlugash, J., Yuceoglu, Y. Z., et al. (1972). New type of cardiomyopathy associated with diabetic glomerulosclerosis. The American Journal of Cardiology, 30, 595–602. https://doi.org/10.1016/0002-9149(72)90595-4.

    Article  CAS  PubMed  Google Scholar 

  9. Kannel, W. B., Hjortland, M., & Castelli, W. P. (1974). Role of diabetes in congestive heart failure: The Framingham study. The American Journal of Cardiology, 34, 29–34. https://doi.org/10.1016/0002-9149(74)90089-7.

    Article  CAS  PubMed  Google Scholar 

  10. 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 

  11. Verma, S. K., Garikipati, V. N. S., & Kishore, R. (2017). Mitochondrial dysfunction and its impact on diabetic heart. Biochim Biophys Acta - Mol Basis Dis, 1863, 1098–1105. https://doi.org/10.1016/j.bbadis.2016.08.021.

    Article  CAS  PubMed  Google Scholar 

  12. King, A. J. (2012). The use of animal models in diabetes research. British Journal of Pharmacology, 166, 877–894. https://doi.org/10.1111/J.1476-5381.2012.01911.X.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Rees, D. A., & Alcolado, J. C. (2005). Animal models of diabetes mellitus. Diabetic Medicine, 22, 359–370. https://doi.org/10.1111/j.1464-5491.2005.01499.x.

    Article  CAS  PubMed  Google Scholar 

  14. Makino, S., Kunimoto, K., Muraoka, Y., et al. (1980). Breeding of a non-obese, diabetic strain of mice. Jikken Dobutsu, 29, 1–13.

    CAS  PubMed  Google Scholar 

  15. Kachapati, K., Adams, D., Bednar, K., & Ridgway, W. M. (2012). The non-obese diabetic (NOD) mouse as a model of human type 1 diabetes. In Animal models in diabetes research (pp. 3–16). Totowa: Humana Press.

    Chapter  Google Scholar 

  16. Driver, J. P., Serreze, D. V., & Chen, Y.-G. (2011). Mouse models for the study of autoimmune type 1 diabetes: A NOD to similarities and differences to human disease. Seminars in Immunopathology, 33, 67–87. https://doi.org/10.1007/s00281-010-0204-1.

    Article  CAS  PubMed  Google Scholar 

  17. Prochazka, M., Serreze, D. V., Frankel, W. N., & Leiter, E. H. (1992). NOR/Lt mice: MHC-matched diabetes-resistant control strain for NOD mice. Diabetes, 41, 98–106. https://doi.org/10.2337/diab.41.1.98.

    Article  CAS  PubMed  Google Scholar 

  18. The Jackson Laboratory (2019) Diabetes onset in NOD/ShiLtJ. https://www.jax.org/jax-mice-and-services/strain-data-sheet-pages/diabetes-chart-001976. Accessed 15 Mar 2019.

  19. López Alarcón, M. M., Rodríguez de Yurre, A., Felice, J. I., et al. (2019). Phase 1 repolarization rate defines Ca2+ dynamics and contractility on intact mouse hearts. The Journal of General Physiology, 151, 771–785. https://doi.org/10.1085/jgp.201812269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Affourtit, C., & Brand, M. D. (2008). Uncoupling protein-2 contributes significantly to high mitochondrial proton leak in INS-1E insulinoma cells and attenuates glucose-stimulated insulin secretion. The Biochemical Journal, 409, 199–204. https://doi.org/10.1042/BJ20070954.

    Article  CAS  PubMed  Google Scholar 

  21. Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. The Journal of Biological Chemistry, 193, 265–275. https://doi.org/10.1016/0922-338X(96)89160-4.

    Article  CAS  PubMed  Google Scholar 

  22. Pesta, D., & Gnaiger, E. (2012). High-resolution respirometry: OXPHOS protocols for human cells and permeabilized fibers from small biopsies of human muscle. Methods in Molecular Biology, 810, 25–58. https://doi.org/10.1007/978-1-61779-382-0_3.

    Article  CAS  PubMed  Google Scholar 

  23. Aguilar-Sanchez, Y., Fainstein, D., Mejia-Alvarez, R., & Escobar, A. L. (2017). Local field fluorescence microscopy: Imaging cellular signals in intact hearts. Journal of Visualized Experiments, e55202–e55202. https://doi.org/10.3791/55202.

  24. Mejía-Alvarez, R., Manno, C., Villalba-Galea, C. A., et al. (2003). Pulsed local-field fluorescence microscopy: A new approach for measuring cellular signals in the beating heart. Pflügers Archiv: European Journal of Physiology, 445, 747–758. https://doi.org/10.1007/s00424-002-0963-1.

    Article  CAS  PubMed  Google Scholar 

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

  26. Flarsheim, C. E., Grupp, I. L., & Matlib, M. A. (1996). Mitochondrial dysfunction accompanies diastolic dysfunction in diabetic rat heart. American Journal of Physiology - Heart and Circulatory Physiology, 40. https://doi.org/10.1152/ajpheart.1996.271.1.h192.

  27. Shen, X., Zheng, S., Thongboonkerd, V., et al. (2004). Cardiac mitochondrial damage and biogenesis in a chronic model of type 1 diabetes. American Journal of Physiology-Endocrinology and Metabolism, 287. https://doi.org/10.1152/ajpendo.00047.2004.

  28. Monnerat, G., Alarcón, M. L., Vasconcellos, L. R., et al. (2016). Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice. Nature Communications, 7. https://doi.org/10.1038/ncomms13344.

  29. Suys, B. E., Huybrechts, S. J. A., De Wolf, D., et al. (2002). QTc interval prolongation and QTc dispersion in children and adolescents with type 1 diabetes. The Journal of Pediatrics, 141, 59–63.

    Article  Google Scholar 

  30. Gill, G. V., Woodward, A., Casson, I. F., & Weston, P. J. (2009). Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes—The ‘dead in bed’ syndrome revisited. Diabetologia, 52, 42–45. https://doi.org/10.1007/s00125-008-1177-7.

    Article  CAS  PubMed  Google Scholar 

  31. Tu, E., Twigg, S. M., & Semsarian, C. (2010). Sudden death in type 1 diabetes: The mystery of the ‘dead in bed’ syndrome. International Journal of Cardiology, 138, 91–93. https://doi.org/10.1016/j.ijcard.2008.06.021.

    Article  PubMed  Google Scholar 

  32. Alarcon, M. M. L., Trentin-Sonoda, M., Panico, K., et al. (2019). Cardiac arrhythmias after renal I/R depend on IL-1β. Journal of Molecular and Cellular Cardiology, 131, 101–111. https://doi.org/10.1016/j.yjmcc.2019.04.025.

    Article  CAS  PubMed  Google Scholar 

  33. Dong, B., Qi, D., Yang, L., et al. (2012). TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the nonobese diabetic mouse model of type 1 diabetes. American Journal of Physiology and Circulatory Physiology, 303, H732–H742. https://doi.org/10.1152/ajpheart.00948.2011.

    Article  CAS  Google Scholar 

  34. Elliott, J. F., Liu, J., Yuan, Z. N., et al. (2003). Autoimmune cardiomyopathy and heart block develop spontaneously in HLA-DQ8 transgenic IAβ knockout NOD mice. Proceedings of the National Academy of Sciences of the United States of America, 100, 13447–13452. https://doi.org/10.1073/pnas.2235552100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Aasa, K. L., Kwong, K. K., Adams, M. A., & Croy, B. A. (2013). Analysis of maternal and fetal cardiovascular systems during hyperglycemic pregnancy in the nonobese diabetic mouse. Biology of Reproduction, 88, 151–151. https://doi.org/10.1095/biolreprod.112.105759.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Rendon, D. A. (2015). The bioenergetics of isolated mitochondria from different animal models for diabetes. Current Diabetes Reviews, 12, 66–80. https://doi.org/10.2174/1573399811666150427163840.

    Article  CAS  Google Scholar 

  37. Pham, T., Loiselle, D., Power, A., & Hickey, A. J. R. (2014). Mitochondrial inefficiencies and anoxic ATP hydrolysis capacities in diabetic rat heart. American Journal of Physiology-Cell Physiology, 307, C499–C507. https://doi.org/10.1152/ajpcell.00006.2014.

    Article  CAS  PubMed  Google Scholar 

  38. Lumini-Oliveira, J., Magalhães, J., Pereira, C. V., et al. (2011). Endurance training reverts heart mitochondrial dysfunction, permeability transition and apoptotic signaling in long-term severe hyperglycemia. Mitochondrion, 11, 54–63. https://doi.org/10.1016/j.mito.2010.07.005.

    Article  CAS  PubMed  Google Scholar 

  39. Babsky, A., Doliba, N., Doliba, N., et al. (2001). Na+ effects on mitochondrial respiration and oxidative phosphorylation in diabetic hearts. Experimental Biology and Medicine (Maywood, N.J.), 226, 543–551. https://doi.org/10.1177/153537020122600606.

    Article  CAS  Google Scholar 

  40. Moreira, P. I., Rolo, A. P., Sena, C., et al. (2006). Insulin attenuates diabetes-related mitochondrial alterations: A comparative study. Medicinal Chemistry, 2, 299–308. https://doi.org/10.2174/157340606776930754.

    Article  CAS  PubMed  Google Scholar 

  41. Herlein, J. A., Fink, B. D., O’Malley, Y., & Sivitz, W. I. (2009). Superoxide and respiratory coupling in mitochondria of insulin-deficient diabetic rats. Endocrinology, 150, 46–55. https://doi.org/10.1210/en.2008-0404.

    Article  CAS  PubMed  Google Scholar 

  42. Preis, S. R., Pencina, M. J., Hwang, S. J., et al. (2009). Trends in cardiovascular disease risk factors in individuals with and without diabetes mellitus in the Framingham heart study. Circulation, 120, 212–220. https://doi.org/10.1161/CIRCULATIONAHA.108.846519.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Kannel, W. B., & McGee, D. L. (1979). Diabetes and cardiovascular risk factors: The Framingham study. Circulation, 59, 8–13. https://doi.org/10.1161/01.CIR.59.1.8.

    Article  CAS  PubMed  Google Scholar 

  44. Rossing, P., Breum, L., Major-Pedersen, A., et al. (2001). Prolonged QTc interval predicts mortality in patients with type 1 diabetes mellitus. Diabetic Medicine, 18, 199–205. https://doi.org/10.1046/j.1464-5491.2001.00446.x.

    Article  CAS  PubMed  Google Scholar 

  45. Stettler, C., Bearth, A., Allemann, S., et al. (2007). QTc interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: A 23-year follow-up. Diabetologia, 50, 186–194. https://doi.org/10.1007/s00125-006-0483-1.

    Article  CAS  PubMed  Google Scholar 

  46. Agashe, S., & Petak, S. (2018). Cardiac autonomic neuropathy in diabetes mellitus. Methodist DeBakey Cardiovascular Journal, 14, 251–256.

    PubMed  PubMed Central  Google Scholar 

  47. Özgür, S., Ceylan, Ö., Şenocak, F., et al. (2013). An evaluation of heart rate variability and its modifying factors in children with type 1 diabetes. Cardiology in the Young, 24, 872–879. https://doi.org/10.1017/S1047951113001224.

    Article  PubMed  Google Scholar 

  48. Vinik, A. I., & Ziegler, D. (2007). Diabetic cardiovascular autonomic neuropathy. Circulation, 115, 387–397.

    Article  Google Scholar 

  49. Kardelen, F., Akçurin, G., Ertug, H., et al. (2006). Heart rate variability and circadian variations in type 1 diabetes mellitus. Pediatric Diabetes, 7, 45–50. https://doi.org/10.1111/j.1399-543X.2006.00141.x.

    Article  PubMed  Google Scholar 

  50. Jaiswal, M., Urbina, E. M., Wadwa, R. P., et al. (2013). Reduced heart rate variability among youth with type 1 diabetes: The SEARCH CVD study. Diabetes Care, 36, 157–162. https://doi.org/10.2337/dc12-0463.

    Article  CAS  PubMed  Google Scholar 

  51. Helleputte, S., De Backer, T., Lapauw, B., et al. (2020). The relationship between glycaemic variability and cardiovascular autonomic dysfunction in patients with type 1 diabetes: A systematic review. Diabetes/Metabolism Research and Reviews.

  52. Jaiswal, M., Fingerlin, T. E., Urbina, E. M., et al. (2013). Impact of glycemic control on heart rate variability in youth with type 1 diabetes: The SEARCH CVD study. Diabetes Technology & Therapeutics, 15, 977–983. https://doi.org/10.1089/dia.2013.0147.

    Article  CAS  Google Scholar 

  53. Gross, V., Tank, J., Partke, H. J., et al. (2008). Cardiovascular autonomic regulation in non-obese diabetic (NOD) mice. Autonomic Neuroscience: Basic and Clinical, 138, 108–113. https://doi.org/10.1016/j.autneu.2007.11.006.

    Article  CAS  Google Scholar 

  54. Moraes, O. A., Colucci, J. A., Souza, L. E., et al. (2013). Cardiovascular autonomic dysfunction in non-obese diabetic mice. Autonomic Neuroscience: Basic and Clinical, 177, 143–147. https://doi.org/10.1016/j.autneu.2013.03.011.

    Article  Google Scholar 

  55. Fazan, R., Dias Da Silva, V. J., Ballejo, G., & Salgado, H. C. (1999). Power spectra of arterial pressure and heart rate in streptozotocin-induced diabetes in rats. Journal of Hypertension, 17, 489–495. https://doi.org/10.1097/00004872-199917040-00006.

    Article  PubMed  Google Scholar 

  56. Dall’Ago, P., Silva, V. O. K., De Angelis, K. L. D., et al. (2002). Reflex control of arterial pressure and heart rate in short-term streptozotocin diabetic rats. Brazilian Journal of Medical and Biological Research, 35, 843–849. https://doi.org/10.1590/S0100-879X2002000700013.

    Article  PubMed  Google Scholar 

  57. Maeda CY, Fernandes TG, Timm HB, Irigoyen MC (1995) Autonomic dysfunction in short-term experimental diabetes. In: Hypertension. pp 1100–1104.

  58. Chen, Y. G., Mathews, C. E., & Driver, J. P. (2018). The role of NOD mice in type 1 diabetes research: Lessons from the past and recommendations for the future. Frontiers in Endocrinology (Lausanne), 9, 1–13. https://doi.org/10.3389/fendo.2018.00051.

    Article  Google Scholar 

  59. Anderson, M. S., & Bluestone, J. A. (2005). THE NOD MOUSE: A model of immune dysregulation. Annual Review of Immunology, 23, 447–485. https://doi.org/10.1146/annurev.immunol.23.021704.115643.

    Article  CAS  PubMed  Google Scholar 

  60. Chaparro, R. J., & Dilorenzo, T. P. (2010). An update on the use of NOD mice to study autoimmune (type 1) diabetes. Expert Review of Clinical Immunology, 6, 939–955. https://doi.org/10.1586/eci.10.68.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Hattori, M., Buse, J. B., Jackson, R. A., et al. (1986). The NOD mouse: Recessive diabetogenic gene in the major histocompatibility complex. Science, 231(80), 733–735. https://doi.org/10.1126/science.3003909.

    Article  CAS  PubMed  Google Scholar 

  62. Pearson, J. A., Wong, F. S., & Wen, L. (2016). The importance of the non obese diabetic (NOD) mouse model in autoimmune diabetes. Journal of Autoimmunity, 66, 76–88.

    Article  CAS  Google Scholar 

  63. Noble, J. A., & Erlich, H. A. (2012). Genetics of type 1 diabetes. Cold Spring Harbor Perspectives in Medicine, 2. https://doi.org/10.1101/cshperspect.a007732.

  64. Reed, J. C., & Herold, K. C. (2015). Thinking bedside at the bench: The NOD mouse model of T1DM. Nature Reviews. Endocrinology, 11, 308–314. https://doi.org/10.1038/nrendo.2014.236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Chatenoud, L., Thervet, E., Primo, J., & Bach, J. F. (1994). Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proceedings of the National Academy of Sciences of the United States of America, 91, 123–127. https://doi.org/10.1073/pnas.91.1.123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Wilson, C. S., Chhabra, P., Marshall, A. F., et al. (2018). Healthy donor polyclonal IgMs diminish B-lymphocyte autoreactivity, enhance regulatory T-cell generation, and reverse type 1 diabetes in NOD mice. Diabetes, 67, 2349–2360. https://doi.org/10.2337/db18-0456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors want to thank Professor Ariel Escobar from University of California - Merced who gave us several and valuable supports to perform recordings in intact hearts and for installing a whole LFFM setup in our laboratory.

Funding

This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-PROCAD no. 88887.124150/2014-00), the Brazilian National Research Council (CNPq no. 306004/2015-1 and CNPq no.141178/2018-3), the Carlos Chagas Filho Rio de Janeiro State Research Foundation (FAPERJ no. 232724), the National Institutes of Science and Technology for Biology Structural and Bioimaging and National Institutes of Science and Technology for Regenerative Medicine (no. 573767/2008-4 and no. 465656/2014-5).

Author information

Author notes

  1. Ygor Schleier and Oscar Moreno-Loaiza contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Cardioimmunology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Ygor Schleier, Oscar Moreno-Loaiza, Maria Micaela López Alarcón, Eduarda Gabrielle Lopes Martins, Bruno Cabral Braga & Emiliano Horacio Medei

  2. Laboratory of Bioenergetics and Mitochondrial Physiology, Institute of Medical Biochemistry Leopoldo de Meis, Center for Health Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Eduarda Gabrielle Lopes Martins & Antonio Galina

  3. National Center for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Isalira Peroba Ramos & Emiliano Horacio Medei

  4. Carlos Chagas Filho Biophysics Institute – UFRJ, Avenida Carlos Chagas Filho, 373-CCS-Bloco G, Rio de Janeiro, RJ, 21941-902, Brazil

    Emiliano Horacio Medei

Authors
  1. Ygor Schleier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Oscar Moreno-Loaiza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Micaela López Alarcón
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eduarda Gabrielle Lopes Martins
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bruno Cabral Braga
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Isalira Peroba Ramos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Antonio Galina
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Emiliano Horacio Medei
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

EM and AG designed the study. YS, OML, MLA, EGLM, BCB, and IPR performed and analyzed the experiments. All authors participated in analysis and interpretation of the results. YS, OML, and EM wrote the manuscript. MLA, EGLM, BCB, IPR, and AG critically reviewed the manuscript for intellectual content. All the authors approved the final version of the manuscript.

Corresponding author

Correspondence to Emiliano Horacio Medei.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and institutional guidelines for the care and use of laboratory animals were followed. The experimental protocols used in this study were approved by the Experimental Animals Ethics Committee of the UFRJ, under protocol number 171/18.

Additional information

Associate Editor Yihua Bei oversaw the review of this article

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schleier, Y., Moreno-Loaiza, O., López Alarcón, M.M. et al. NOD Mice Recapitulate the Cardiac Disturbances Observed in Type 1 Diabetes. J. of Cardiovasc. Trans. Res. 14, 271–282 (2021). https://doi.org/10.1007/s12265-020-10039-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-020-10039-y

Keywords

Search

Navigation