Lizzi L, Massimi M. Letter to the Editor: Tumor necrosis factor-α signaling and β-cell apoptosis in acute pancreatitis - integrating molecular mechanisms and metabolic implications. World J Gastroenterol 2026; 32(27): 117268 [DOI: 10.3748/wjg.117268]
Corresponding Author of This Article
Mara Massimi, PhD, Associate Professor, Department of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, L'Aquila 67100, AQ, Italy. mara.massimi@univaq.it
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Research & Experimental Medicine
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letter
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Lizzi L, Massimi M. Letter to the Editor: Tumor necrosis factor-α signaling and β-cell apoptosis in acute pancreatitis - integrating molecular mechanisms and metabolic implications. World J Gastroenterol 2026; 32(27): 117268 [DOI: 10.3748/wjg.117268]
World J Gastroenterol. Jul 21, 2026; 32(27): 117268 Published online Jul 21, 2026. doi: 10.3748/wjg.117268
Letter to the Editor: Tumor necrosis factor-α signaling and β-cell apoptosis in acute pancreatitis - integrating molecular mechanisms and metabolic implications
Lara Lizzi, Mara Massimi
Lara Lizzi, Mara Massimi, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila 67100, AQ, Italy
Author contributions: Massimi M conceived the overall concept and outline, drafted the manuscript, and supervised the work; Lizzi L contributed to the development of the figure and to the discussion and literature review. Both authors critically revised the manuscript and approved the final version.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Corresponding author: Mara Massimi, PhD, Associate Professor, Department of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, L'Aquila 67100, AQ, Italy. mara.massimi@univaq.it
Received: December 3, 2025 Revised: December 23, 2025 Accepted: February 10, 2026 Published online: July 21, 2026 Processing time: 213 Days and 13.6 Hours
Abstract
The recent study by Chen et al, published in the World Journal of Gastroenterology, provides valuable evidence that tumor necrosis factor-α (TNF-α) contributes to acute metabolic disorder after acute pancreatitis through Bax/Bcl-2-mediated β-cell apoptosis. Their study elegantly combines clinical observations with experimental data, but the biological framework underlying TNF-α signaling in β-cell damage is more complex than a single apoptotic pathway. TNF-α appears to function as a central hub, linking nuclear factor kappa B (NF-κB) activation, oxidative and endoplasmic reticulum stress, and cytokine cross-talk, all of which influence β-cell survival. The apoptotic cascade described by Chen et al can be viewed as one effector branch of this wider network. Moreover, TNF-α affects key metabolic aspects of β-cell function, including mitochondrial activity and GLUT2-dependent glucose handling, suggesting that metabolic dysfunction and apoptosis may arise together as part of an integrated stress response. By briefly outlining these additional mechanisms, this article places TNF-α within a broader inflammatory-metabolic context that complements and extends their interpretation.
Core Tip: Tumor necrosis factor-α (TNF-α) contributes to dysglycemia after acute pancreatitis not only by activating apoptotic pathways, but also by coordinating a broader network of inflammatory, oxidative, endoplasmic reticulum stress, and metabolic signals that impair β-cell function. Recognizing TNF-α as an upstream integrator, rather than a single apoptotic trigger, helps explain the heterogeneity of post-pancreatitis dysglycemia and highlights new therapeutic opportunities aimed at enhancing β-cell metabolic resilience.
