Exercise-Mediated Regulation of Pyroptosis in Diabetes and Its Complications: Molecular Mechanisms and Translational Perspectives
4 affiliations
- 1School of Sports Science, Qufu Normal University, Qufu 273165, China
- 2School of Life Sciences, Nanjing University, Nanjing 210023, China
- 3School of Humanities and Social Sciences, Shanghai Lida University, Shanghai 201609, China
- 4School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China
Abstract
Diabetes mellitus (DM) is characterized by chronic metabolic stress and low-grade inflammation that progressively damage multiple organs. Pyroptosis, a gasdermin-mediated form of inflammatory regulated cell death, may connect hyperglycemia, lipotoxicity, oxidative stress, mitochondrial dysfunction, and inflammasome activation to tissue injury. This review synthesizes evidence for pyroptosis in pancreatic β cells, adipose tissue, the liver, heart, kidneys, skeletal muscle, bone, retina, nervous system, and lungs, and critically evaluates how exercise may modulate these processes. Exercise improves metabolic and mitochondrial homeostasis; reduces reactive oxygen species, oxidized mitochondrial DNA, and extracellular adenosine triphosphate; and regulates thioredoxin-interacting protein/NLRP3, P2X/pannexin 1, and cyclic GMP-AMP synthase-stimulator of interferon genes signaling. Exercise-induced factors, including irisin, meteorin-like protein, and adropin, may further mediate cross-organ communication. The most direct antipyroptotic evidence currently concerns diabetic cardiomyopathy, muscle atrophy, and osteoporosis, whereas studies of adipose tissue, metabolic dysfunction-associated steatotic liver disease, and diabetic kidney disease often demonstrate inflammasome suppression without establishing gasdermin-dependent membrane lysis. Clinical benefits therefore cannot yet be attributed directly to pyroptosis inhibition. Standardized exercise protocols, cell-specific models, complete pyroptosis evidence chains, and clinically applicable biomarkers are required to translate these mechanisms into precision exercise prescriptions.
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BibTeX
@article{li2026exercisemediated,
title = {{Exercise-Mediated Regulation of Pyroptosis in Diabetes and Its Complications: Molecular Mechanisms and Translational Perspectives}},
author = {Junzhe Li and Ze Wang and Danlin Zhu and Haoyang Gao and Junyu Wang},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16111577},
url = {https://www.mdpi.com/2218-273X/16/11/1577},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Exercise-Mediated Regulation of Pyroptosis in Diabetes and Its Complications: Molecular Mechanisms and Translational Perspectives
AU - Junzhe Li
AU - Ze Wang
AU - Danlin Zhu
AU - Haoyang Gao
AU - Junyu Wang
PY - 2026
DA - 2026/10/29
JO - Biomolecules
DO - 10.3390/biom16111577
UR - https://www.mdpi.com/2218-273X/16/11/1577
AB - Diabetes mellitus (DM) is characterized by chronic metabolic stress and low-grade inflammation that progressively damage multiple organs. Pyroptosis, a gasdermin-mediated form of inflammatory regulated cell death, may connect hyperglycemia, lipotoxicity, oxidative stress, mitochondrial dysfunction, and inflammasome activation to tissue injury. This review synthesizes evidence for pyroptosis in pancreatic β cells, adipose tissue, the liver, heart, kidneys, skeletal muscle, bone, retina, nervous system, and lungs, and critically evaluates how exercise may modulate these processes. Exercise improves metabolic and mitochondrial homeostasis; reduces reactive oxygen species, oxidized mitochondrial DNA, and extracellular adenosine triphosphate; and regulates thioredoxin-interacting protein/NLRP3, P2X/pannexin 1, and cyclic GMP-AMP synthase-stimulator of interferon genes signaling. Exercise-induced factors, including irisin, meteorin-like protein, and adropin, may further mediate cross-organ communication. The most direct antipyroptotic evidence currently concerns diabetic cardiomyopathy, muscle atrophy, and osteoporosis, whereas studies of adipose tissue, metabolic dysfunction-associated steatotic liver disease, and diabetic kidney disease often demonstrate inflammasome suppression without establishing gasdermin-dependent membrane lysis. Clinical benefits therefore cannot yet be attributed directly to pyroptosis inhibition. Standardized exercise protocols, cell-specific models, complete pyroptosis evidence chains, and clinically applicable biomarkers are required to translate these mechanisms into precision exercise prescriptions.
SN - 2218-273X
ER -