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Review
. 2021 May 24:14:2187-2206.
doi: 10.2147/JIR.S291453. eCollection 2021.

Role of Pyroptosis in Diabetes and Its Therapeutic Implications

Abdullah Al Mamun  1 , Yanqing Wu  2 , Fatema Nasrin  3   4 , Afroza Akter  5 , Masuma Afrin Taniya  6 , Fahad Munir  7 , Chang Jia  8 , Jian Xiao  1
Affiliations
Review

Role of Pyroptosis in Diabetes and Its Therapeutic Implications

Abdullah Al Mamun et al. J Inflamm Res. .

Abstract

Pyroptosis is mainly considered as a new pro-inflammatory mediated-programmed cell death. In addition, pyroptosis is described by gasdermin-induced pore formation on the membrane, cell swelling and rapid lysis, and several pro-inflammatory mediators interleukin-1β (IL-1β) and interleukin-18 (IL-18) release. Extensive studies have shown that pyroptosis is commonly involved by activating the caspase-1-dependent canonical pathway and caspase-4/5/11-dependent non-canonical pathway. However, pyroptosis facilitates local inflammation and inflammatory responses. Current researches have reported that pyroptosis promotes the progression of several diabetic complications. Emerging studies have suggested that some potential molecules targeting the pyroptosis and inflammasome signaling pathways could be a novel therapeutic avenue for managing and treating diabetes and its complications in the near future. Our narrative review concisely describes the possible mechanism of pyroptosis and its progressive understanding of the development of diabetic complications.

Keywords: GSDMD; IL-18; IL-1β; NLRP3; caspase-1; diabetes; pyroptosis.

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Conflict of interest statement

The authors reported no conflicts of interest for this work.

Figures

Figure 1
Figure 1
Molecular mechanisms of pyroptosis-regulated cell death. Pyroptosis-signaling pathways are generally activated by the stimulation of DAMPs or PAMPs triggering several inflammasomes. The stimulated inflammasome components trigger the cleavage of caspase-1. Caspase-1 can significantly cleave GSDMD to form GSDMD N-fragment and plasma membrane pores formation, leading to pyroptosis-regulated cell death. Stimulated caspase-1 leads to the maturation and secretion of IL-1β and IL-18 inflammatory factors. Besides, LPS binds to the caspase-4/5/11 precursor, leading to the activation of pyroptosis-regulated cell death. Caspase-3/GSDME can also lead to pyroptosis-regulated cell death. Notably, mitochondrial and death receptor pathways can trigger caspase-3. Then, the activated caspase-3 cleaves GSDME to form GSDME N-fragments, leading to plasma membrane pores formation, cell swelling, and pyroptosis.
Figure 2
Figure 2
Activating the caspase-1/4/5/8/11 signaling pathways, inflammatory factors including IL-1β and IL-18 release, and ROS generation, leading to GSDMD/GSDME-mediated pore formation as well as cell lysis and promote the development of diabetic complications.
Figure 3
Figure 3
Summary of the pyroptosis in the development of diabetic complications and its therapeutic implications.
See this image and copyright information in PMC

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References

    1. de Candia P, Prattichizzo F, Garavelli S, et al. Type 2 diabetes: how much of an autoimmune disease? Front Endocrinol (Lausanne). 2019;10:451. doi:10.3389/fendo.2019.00451 - DOI - PMC - PubMed
    1. Nowotny K, Jung T, Höhn A, Weber D, Grune T. Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules. 2015;5(1):194–222. doi:10.3390/biom5010194 - DOI - PMC - PubMed
    1. Volpe CMO, Villar-Delfino PH, Dos Anjos PMF, Nogueira-Machado JA. Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis. 2018;9(2):119. - PMC - PubMed
    1. Fiorentino TV, Prioletta A, Zuo P, Folli F. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Curr Pharm Des. 2013;19(32):5695–5703. - PubMed
    1. Jorgensen I, Rayamajhi M, Miao EA. Programmed cell death as a defence against infection. Nat Rev Immunol. 2017;17(3):151–164. - PMC - PubMed