Aims: To investigate the relationship among NLRP3 inflammasome, glucose and lipid metabolism, and insulin resistance (IR) in the serum of patients with diabetes and pre-diabetes. Methods: A total of 100 patients with abnormal blood glucose divided into the pre-diabetes mellitus (PDM) group (N = 46) and the type 2 diabetes mellitus (T2DM) group (N = 54). 20 normoglycemic subjects (NG, N = 20) were selected as a control group. The serum levels of glucose and lipid metabolism, IR, and the expression of NLRP3, ASC and Caspase-1 were measured. Besides, the correlations of NLRP3 inflammasome with glucose and lipid metabolism, and IR were analyzed. Results: Compared with the NG group, the levels of NLRP3, ASC, Caspase-1, FBG, HbA1C, TG, LDL-C, FINs, and HOMA-IR were higher (P < 0.05), while the contents of HDL-C and HOMA-β were lower (P < 0.05) in the serum of both PDM and T2DM groups. Elevated levels of NLRP3, ASC, Caspase-1, FBG, HbA1C, FINs, and HOMA-IR were detected (P < 0.05), while decreased contents of HDL-C and HOMA-β were seen (P < 0.05) in T2DM group when compared with those in the PDM group. Correlation analysis found that activation of NLRP3 inflammasome was positively correlated with the concentrations of HbA1C, FINs, and HOMA-IR (P < 0.05), but negatively correlated with HDL-C and HOMA-β. Regression analysis further showed that blood glucose related indexes, FINs, and NLRP3 have made a decisive contribution to IR. Conclusions: Collectively, this evidence suggested that NLRP3 is closely related to glucose and lipid metabolism, and IR, and activated in PDM and T2DM.
References
[1]
Saeedi, P., Petersohn, I., Salpea, P., et al. (2019) Global and Regional Diabetes Prevalence Estimates for 2019 and Projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th Edition. Diabetes Research and Clinical Practice, 157, Article ID: 107843. https://doi.org/10.1016/j.diabres.2019.107843
[2]
Chinese Society of Endocrinology, Chinese Medical Association Diabetes Branch, Endocrinology and Metabolism Physician Branch of Chinese Medical Doctor Association, Endocrinology and Metabolism Branch of Chinese Research Hospital Association and Diabetes Branch of Chinese Research Hospital Association (2020) Expert Consensus on Adult Prediabetes Intervention in China. Chinese Journal of Endocrinology and Metabolism, 36, 371-380. (In Chinese) https://doi.org/10.3760/cma.j.cn311282-20200115-00022
[3]
Azemi, A.K., Mokhtar, S.S., Hou, L.J., Sharif, S.E.T. and Rasool, A.H.G. (2021) Model for Type 2 Diabetes Exhibits Changes in Vascular Function and Structure Due to Vascular Oxidative Stress and Inflammation. Biotechnic & Histochemistry, 96, 498-506. https://doi.org/10.1080/10520295.2020.1823480
[4]
Jiang, H and Zhou, R.B. (2016) NLRP3 Inflammasome: A Novel Target for T2DM Treatment? Chinese Science Bulletin, 61, 3541-3547. (In Chinese) https://doi.org/10.1360/N972016-00653
[5]
Hu, S., Hu, Y., Long, P., et al. (2022) The Effect of Tai Chi Intervention on NLRP3 and Its Related Antiviral Inflammatory Factors in the Serum of Patients with Pre-Diabetes. Frontiers in Immunology, 13, Article 1026509. https://doi.org/10.3389/fimmu.2022.1026509
[6]
Liang, F., Huang, T., Li, B., et al. (2020) High-Intensity Interval Training and Moderate-Intensity Continuous Training Alleviate β-Amyloid Deposition by Inhibiting NLRP3 Inflammasome Activation in APPswe/PS1dE9 Mice. NeuroReport, 31, 425-432. https://doi.org/10.1097/WNR.0000000000001429
[7]
Wang, X., Yang, Y., Cai, W.-Q. and Lu, Y. (2020) The Relationship of Sphingosine Kinase 1 with Pyroptosis Provides a New Strategy for Tumor Therapy. Frontiers in Immunology, 11, Article 574990. https://doi.org/10.3389/fimmu.2020.574990
Rheinheimer, J., De Souza, B.M., Cardoso, N.S., Bauer, A.C. and Crispim, D. (2017) Current Role of the NLRP3 Inflammasome on Obesity and Insulin Resistance: A Systematic Review. Metabolism, 74, 1-9. https://doi.org/10.1016/j.metabol.2017.06.002
[10]
Yang, N., Zhang, H.B. and Li, Y.X. (2019) Interpretation on the Update of American Diabetes Association Standards of Medical Care in Diabetes—2019. Medical Journal of Peking Union Medical College Hospital, 10, 476-480. (In Chinese) https://doi.org/10.3969/j.issn.1674-9081.2019.05.009
[11]
Matthews, D.R., Hosker, J.P., Rudenski, A.S., et al. (1985) Homeostasis Model Assessment: Insulin Resistance and β-Cell Function from Fasting Plasma Glucose and Insulin Concentrations in Man. Diabetologia, 28, 412-419. https://doi.org/10.1007/BF00280883
[12]
Wang, Y., Zhong, J., Zhang, X., et al. (2016) The Role of HMGB1 in the Pathogenesis of Type 2 Diabetes. Journal of Diabetes Research, 2016, Article ID: 2543268. https://doi.org/10.1155/2016/2543268
[13]
Zhu, Z.G., Yang, H.Y., Huang, L., et al. (2021) The Correlation of Serum MicroRNA-152 Expression with Lipid Metabolism and Insulin Resistance in Patients with Diabetes Mellitus. China Journal of Modern Medicine, 31, 1-6. (In Chinese) https://doi.org/10.3969/j.issn.1005-8982.2021.08.001
[14]
Hu, S., Wan, X., Li, X. and Wang, X. (2022) Aerobic Exercise Alleviates Pyroptosis-Related Diseases by Regulating NLRP3 Inflammasome. Frontiers in Physiology, 13, Article 965366. https://doi.org/10.3389/fphys.2022.965366
[15]
Brown, E.C., Franklin, B.A., Regensteiner, J.G. and Stewart, K.J. (2020) Effects of Single Bout Resistance Exercise on Glucose Levels, Insulin Action, and Cardiovascular Risk in Type 2 Diabetes: A Narrative Review. Journal of Diabetes and Its Complications, 34, Article ID: 107610. https://doi.org/10.1016/j.jdiacomp.2020.107610
[16]
Luo, B., Li, B., Wang, W., et al. (2014) NLRP3 Gene Silencing Ameliorates Diabetic Cardiomyopathy in a Type 2 Diabetes Rat Model. PLOS ONE, 9, e104771. https://doi.org/10.1371/journal.pone.0104771
[17]
Gora, I.M., Ciechanowska, A. and Ladyzynski, P. (2021) NLRP3 Inflammasome at the Interface of Inflammation, Endothelial Dysfunction, and Type 2 Diabetes. Cells, 10, Article No. 314. https://doi.org/10.3390/cells10020314
[18]
Sepehri, Z., Kiani, Z., Afshari, M., et al. (2017) Inflammasomes and Type 2 Diabetes: An Updated Systematic Review. Immunology Letters, 192, 97-103. https://doi.org/10.1016/j.imlet.2017.10.010
[19]
Ruscitti, P., Cipriani, P., Di Benedetto, P., et al. (2015) Monocytes from Patients with Rheumatoid Arthritis and Type 2 Diabetes Mellitus Display an Increased Production of Interleukin (IL)-1β via the Nucleotide-Binding Domain and Leucine-Rich Repeat Containing Family Pyrin 3(NLRP3)-Inflammasome Activation: A Possible Implication for Therapeutic Decision in These Patients. Clinical and Experimental Immunology, 182, 35-44. https://doi.org/10.1111/cei.12667
