ArticleDiabetology & metabolic syndrome2023
Irisin suppresses pancreatic β cell pyroptosis in T2DM by inhibiting the NLRP3-GSDMD pathway and activating the Nrf2-TrX/TXNIP signaling axis.
Article in Diabetology & metabolic syndrome, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Pooled it
- Irisin Restrains Oligodendroglial Ferroptosis to Preserve White Matter After Traumatic Brain Injury via AMPK Activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Crosstalk of thioredoxin system and programmed cell death: from pathophysiology to novel therapy.Redox biology · 2026Review
- The myokine irisin ameliorates the secretory dysfunction of pancreatic β cells in experimental and human type 2 diabetes.Science advances · 2026Article
- AdipoRon ameliorates vascular endothelial injury in type 2 diabetes mellitus and is associated with suppression of the NLRP3-Caspase-1-GSDMD pyroptosis axis.BMC cardiovascular disorders · 2026Article
- Mitochondria-associated programmed cell death in pancreatic β cell of T2DM.Apoptosis : an international journal on programmed cell death · 2026Review
- Supernatants from Water Extraction-Ethanol Precipitation ofFoods (Basel, Switzerland) · 2026Article
- Molecular insights into irisin's role in the regulation of programmed cell death: mechanisms and therapeutic potential.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Inhibitory effects of the flavonoids extracted from Pollen Typhae on palmitic acid-induced NLRP3 inflammasome activation in macrophages involving AMPK-mediated lipid metabolism.BMC complementary medicine and therapies · 2025Article
- HIIT and MICT mitigate endothelial dysfunction in early atherosclerotic mice via PCSK9 inhibition.Scientific reports · 2025Article
- Irisin regulates integrin αvβ5/FAK/ERK to inhibit neutrophil extracellular traps formation and reduce pancreatic beta-cells pyroptosis in type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2025Article
- Nano-Drug Delivery System Targeting the Oxidative Stress Microenvironment: A Prospective Strategy for Intervertebral Disc Degeneration Treatment.International journal of nanomedicine · 2025Review
- Exercise-produced irisin effects on brain-related pathological conditions.Metabolic brain disease · 2024Review
- Alginate Oligosaccharides Protect Gastric Epithelial Cells against Oxidative Stress Damage through Induction of the Nrf2 Pathway.Antioxidants (Basel, Switzerland) · 2024Article
- FNDC5/irisin ameliorates bone loss of type 1 diabetes by suppressing endoplasmic reticulum stress‑mediated ferroptosis.Journal of orthopaedic surgery and research · 2024Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIrisin plays a key role in metabolic diseases, including type 2 diabetes mellitus (T2DM). However, the mechanism underlying the link between irisin and the development of T2DM, particularly in pancreatic islet β-cells, remains unknown.
methodsIn vitro, Min6 cells were treated with high glucose (HG) to generate T2DM cell models. GSDMD-N staining, Western blotting assays, and ELISA were performed to measure the expression levels of GSDMD, caspase 1, IL-1β, and IL-18. Next, the NLRP3 stimulator, ATP, was used to assess the effect of irisin on NLRP3 inflammasome. To evaluate the function of the Nrf2-TrX/TXNIP signaling axis, the Nrf2 inhibitor ML385 was used. For in vivo assessment, we first established T2DM model mice. Then, hematoxylin and eosin (H&E) staining was performed to observe the islet morphology, and the immunofluorescence technique was used to examine the mass of α and β cells. To confirm the role of the Nrf2-TrX/TXNIP signaling axis, ML385 was injected into the mice. Immunofluorescence of Nrf2, caspase 1, and GSDMD was detected in the islet cells of the model mice to verify the results.
resultsWe found that irisin treatment significantly decreased the expression of GSDMD-N (P31) and cleaved caspase-1 (p20), decreased caspase1 activity, and inhibited the secretion of IL-1β and IL-18 in HG-treated Min6 cells. We also found that irisin inhibited oxidative stress and NLRP3 expression by activating the Nrf2-TrX/TXNIP signaling axis. Additionally, in the T2DM model mice, irisin enhanced the function of islet cells, decreased insulin resistance, and preserved the morphology of pancreatic islets.
conclusionWe showed in this study that irisin can be used for treating pyroptosis in HG-induced islet β-cells and T2DM model mice. We also found that irisin inhibits pyroptosis and oxidative stress by inhibiting the NLRP3-GSDMD pathway and activating the Nrf2-TrX/TXNIP signaling axis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.