The Role of the NLRP3 Inflammasome in Type 1 Diabetes: Insights From a Systematic Literature Review of Rodent Studies

Main Article Content

Razif Abas
Shamala Devi Subramaniam

Abstract

Introduction: Type 1 Diabetes mellitus (T1DM) is an autoimmune disease characterized by the destruction of pancreatic β-cells, necessitating lifelong insulin therapy. The rising incidence of T1DM imposes a significant economic burden worldwide, particularly in countries like Malaysia with high diabetes rates. The NLRP3 inflammasome, crucial for regulating inflammation, has emerged as a potential therapeutic target for T1DM due to its involvement in immune dysfunction and tissue damage. This study reviews existing literature and experimental data to clarify the NLRP3 inflammasome's role in T1DM development and progression. Materials and methods: We conducted a systematic search across five electronic databases (Scopus, Science Direct, Sage Journals, Wiley Online Library, and SpringerLink) from 2000 to 2024 using keywords such as "NLRP3," "inflammasome," "rat," "rabbit," and "mice." Data were extracted using a predefined Excel template, covering study objectives, rodent models, NLRP3 inflammasome treatment, findings, and limitations. A systematic review approach was used to analyze and synthesize the results. Results: The review highlights a consistent upregulation of NLRP3 inflammasome activity in T1DM, suggesting its role in disease pathophysiology. Studies on NLRP3 inhibitor compound (MCC950), showed promising results in reducing neurovascular remodeling, improving cognitive function, and enhancing survival rates post-stroke in diabetic animals. Additionally, NLRP3 inhibition facilitated alveolar bone healing in diabetic rats, indicating its potential in tissue repair and regeneration. Conclusion: Targeting the NLRP3 inflammasome offers a promising strategy for managing T1DM. However, further research is needed to understand its mechanisms fully and to develop therapeutic strategies that improve patient outcomes and address T1DM-related complications.

Downloads

Download data is not yet available.

Article Details

How to Cite
Abas, R., & Subramaniam, S. D. (2025). The Role of the NLRP3 Inflammasome in Type 1 Diabetes: Insights From a Systematic Literature Review of Rodent Studies. Malaysian Journal of Medicine and Health Sciences, 21(3), 457–464. https://doi.org/10.47836/mjmhs.21.3.53
Section
Systematic Reviews

References

Cabrera SM, Henschel AM, Hessner MJ. Innate inflammation in type 1 diabetes. Translational Research. 2016;167(1):214-27. https://doi.org/10.1016/j.trsl.2015.04.011

Mordes JP, Bortell R, Blankenhorn EP, Rossini AA, Greiner DL. Rat models of type 1 diabetes: genetics, environment, and autoimmunity. ILAR journal. 2004;45(3):278-91. https://doi.org/10.1093/ilar.45.3.278

Kim S-M, Lee S-H, Kim Y-G, Kim S-Y, Seo J-W, Choi Y-W, et al. Hyperuricemia-induced NLRP3 activation of macrophages contributes to the progression of diabetic nephropathy. American Journal of Physiology-Renal Physiology. 2015;308(9):F993-F1003. https://doi.org/10.1152/ajprenal.00637.2014

Vlad A, Timar R. Pathogenesis of Type 1 diabetes mellitus: a brief overview. Romanian Journal of Diabetes Nutrition and Metabolic Diseases. 2012;19(1):67-72.

Ganasegeran K, Hor CP, Jamil MFA, Suppiah PD, Noor JM, Hamid NA, et al. Mapping the scientific landscape of diabetes research in Malaysia (2000–2018): A systematic scientometrics study. International journal of environmental research and public health. 2021;18(1):318. https://doi.org/10.3390/ijerph18010318

Akhtar S, Nasir JA, Ali A, Asghar M, Majeed R, Sarwar A. Prevalence of type-2 diabetes and prediabetes in Malaysia: A systematic review and meta-analysis. PloS one. 2022;17(1):e0263139. https://doi.org/10.1371/journal.pone.0263139

Sun X, Pang H, Li J, Luo S, Huang G, Li X, et al. The NLRP3 inflammasome and its role in T1DM. Frontiers in Immunology. 2020;11:1595. https://doi.org/10.3389/fimmu.2020.01595

Pereira CA, Carlos D, Ferreira NS, Silva JF, Zanotto CZ, Zamboni DS, et al. Mitochondrial DNA promotes NLRP3 inflammasome activation and contributes to endothelial dysfunction and inflammation in type 1 diabetes. Frontiers in Physiology. 2020;10:1557. https://doi.org/10.3389/fphys.2019.01557

Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140(6):805-20. DOI 10.1016/j.cell.2010.01.022

Franchi L, Eigenbrod T, Muñoz-Planillo R, Nuñez G. The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nature immunology. 2009;10(3):241-7. doi:10.1038/ni.1703.

Sharma D, Kanneganti T-D. The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation. Journal of Cell Biology. 2016;213(6):617-29. www.jcb.org/cgi/doi/10.1083/jcb.201602089

Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. International journal of molecular sciences. 2019;20(13):3328. https://doi.org/10.3390/ijms20133328

Razif A, Basir R, Thani SM, Salihan S, Azmah S, Zainal NHM, et al. The Evolving Role of Nucleotide-binding Oligomerisation Domain-like Receptor Pyrin Domain 3 Inflammasome Activation in Vascular Endothelial Cells: A Review. The Malaysian Journal of Medical Sciences: MJMS. 2022;29(2):8. https://doi.org/10.21315/mjms2022.29.2.2

Subramaniam SD, Zain NALM, Woon CK, Syawalina N. Diabetic Cardiac Autonomic Neuropathy: A Review of NLRP3 Inflammasome Complicity. Malaysian Journal of Medicine and Health Sciences. 2024;20(1):365-8. doi:10.47836/mjmhs.20.1.44

Silva-dos-Santos NM, Oliveira-Abreu K, Moreira-Junior L, dos Santos-Nascimento T, da Silva-Alves KS, Coelho-de-Souza AN, et al. Diabetes mellitus alters electrophysiological properties in neurons of superior cervical ganglion of rats. Brain Research. 2020;1729:146599. https://doi.org/10.1016/j.brainres.2019.146599

Carlos D, Costa FR, Pereira CA, Rocha FA, Yaochite JN, Oliveira GG, et al. Mitochondrial DNA activates the NLRP3 inflammasome and predisposes to type 1 diabetes in murine model. Frontiers in Immunology. 2017;8:187998. doi: 10.3389/fimmu.2017.00164

Eizirik DL, Szymczak F, Mallone R. Why does the immune system destroy pancreatic β-cells but not α-cells in type 1 diabetes? Nature Reviews Endocrinology. 2023;19(7):425-34. https://doi.org/10.1038/s41574-023-00826-3

Corcoran SE, Halai R, Cooper MA. Pharmacological inhibition of the nod-like receptor family pyrin domain containing 3 inflammasome with MCC950. Pharmacological reviews. 2021;73(3):968-1000. https://doi.org/10.1124/pharmrev.120.000171

Menini S, Iacobini C, Vitale M, Pugliese G. The inflammasome in chronic complications of diabetes and related metabolic disorders. Cells. 2020;9(8):1812. https://doi.org/10.3390/cells9081812

Swanson KV, Deng M, Ting JP-Y. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nature Reviews Immunology. 2019;19(8):477-89. doi:10.1038/s41577-019-0165-0.

Alyaseer AAA, De Lima MHS, Braga TT. The role of NLRP3 inflammasome activation in the epithelial to mesenchymal transition process during the fibrosis. Frontiers in immunology. 2020;11:532326. https://doi.org/10.3389/fimmu.2020.00883

Yu C, Zhang C, Kuang Z, Zheng Q. The role of NLRP3 inflammasome activities in bone diseases and vascular calcification. Inflammation. 2021;44:434-49. DOI: 10.1007/s10753-020-01357-z

Shaffril HAM, Samah AA, Samsuddin SF, Ali Z. Mirror-mirror on the wall, what climate change adaptation strategies are practiced by the Asian's fishermen of all? Journal of cleaner production. 2019;232:104-17. https://doi.org/10.1016/j.jclepro.2019.05.262

Ward R, Li W, Abdul Y, Jackson L, Dong G, Jamil S, et al. NLRP3 inflammasome inhibition with MCC950 improves diabetes-mediated cognitive impairment and vasoneuronal remodeling after ischemia. Pharmacological research. 2019;142:237-50. doi:10.1016/j.phrs.2019.01.035.

Li H, Zhong X, Chen Z, Li W. Suppression of NLRP3 inflammasome improves alveolar bone defect healing in diabetic rats. Journal of Orthopaedic Surgery and Research. 2019;14:1-7. https://doi.org/10.1186/s13018-019-1215-9

Wu X, Liu Y, Tu D, Liu X, Niu S, Suo Y, et al. Role of NLRP3-inflammasome/caspase-1/galectin-3 pathway on atrial remodeling in diabetic rabbits. Journal of Cardiovascular Translational Research. 2020;13:731-40. https://doi.org/10.1007/s12265-020-09965-8

Liu H, Xu R, Kong Q, Liu J, Yu Z, Zhao C. Downregulated NLRP3 and NLRP1 inflammasomes signaling pathways in the development and progression of type 1 diabetes mellitus. Biomedicine & Pharmacotherapy. 2017;94:619-26. https://doi.org/10.1016/j.biopha.2017.07.102