Tumor necrosis factor-α promotes abnormal glucose metabolism after acute pancreatitis by inducing islet β-cell apoptosis via Bax/Bcl-2/caspase-3 signaling pathway

Sep 28, 2026

Investigates how tumor necrosis factor-α (TNF-α) contributes to abnormal glucose metabolism (AGM) following acute pancreatitis and to post-pancreatitis diabetes risk. Clinical review of 369 acute pancreatitis patients assessed AGM incidence and associated characteristics, while in vitro models used lipopolysaccharide-treated 266-6 acinar cells and MIN-6 β-cells, and an in vivo sodium taurocholate mouse model. Measures included proliferation, apoptosis, protein expression, and TNF-α inhibition effects. Results link AGM with clinical severity, show TNF-α elevation, and identify Bax/Bcl-2/caspase-3 pathway activation with TNF-α blockade reducing apoptosis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Background

Aim

Methods

Results

Conclusion

Key Words

Core Tip

| W | J | G | World Journal of
Gastroenterology | | --- | --- | --- | --- | Submit a Manuscript: [https://www.f6publishing.com](https://www.f6publishing.com) World J Gastroenterol 2025 December 21; 31(47): 113205 DOI: 10.3748/wjg.v31.i47.113205 ISSN 1007-9327 (print) ISSN 2219-2840 (online) ORIGINAL ARTICLE Basic Study Tumor necrosis factor-α promotes abnormal glucose metabolism after acute pancreatitis by inducing islet β-cell apoptosis via Bax/Bcl-2/caspase-3 signaling pathway Hai-Feng Chen, Chen Gong, Ting-Ting Wang, Jian-Xin Zhu, Wei-Ping Li Specialty type: Gastroenterology and hepatology Provenance and peer review: Invited article; Externally peer reviewed. Peer-review model: Single blind Peer-review report’s classification Scientific Quality: Grade B, Grade B Novelty: Grade A, Grade B Creativity or Innovation: Grade B, Grade B Scientific Significance: Grade B, Grade B P-Reviewer: Liu Y, MD, PhD, Postdoctoral Fellow, China; Molasy B, MD, PhD, Assistant Professor, Poland Received: August 19, 2025 Revised: September 29, 2025 Accepted: November 7, 2025 Published online: December 21, 2025 Processing time: 122 Days and 20.3 Hours Hai-Feng Chen, Chen Gong, Jian-Xin Zhu, Department of Gastroenterology, Taicang Affiliated Hospital of Soochow University (The First People’s Hospital of Taicang), Taicang 215400, Jiangsu Province, China Ting-Ting Wang, Department of Nephrology, Taicang Affiliated Hospital of Soochow University (The First People’s Hospital of Taicang), Taicang 215400, Jiangsu Province, China Wei-Ping Li, Department of Gastrointestinal Surgery, Taicang Affiliated Hospital of Soochow University (The First People’s Hospital of Taicang), Suzhou 215400, Jiangsu Province, China Co-first authors: Hai-Feng Chen and Chen Gong. Co-corresponding authors: Ting-Ting Wang and Wei-Ping Li. Corresponding author: Wei-Ping Li, Department of Gastrointestinal Surgery, Taicang Affiliated Hospital of Soochow University (The First People’s Hospital of Taicang), No. 58 South Changsheng Road, Suzhou 215400, Jiangsu Province, [China.](China. question12397@163.com)[ question12397@163.com](China. question12397@163.com) Abstract BACKGROUND Tumor necrosis factor-α (TNF-α) has been implicated in the development of diabetes following chronic pancreatitis. However, its role in abnormal glucose metabolism (AGM) after acute pancreatitis (AP) and post-pancreatitis diabetes mellitus remains unclear. AIM To investigate the role of TNF-α in AP-associated AGM and its effects on islet β -cell apoptosis, focusing on the underlying molecular mechanisms. METHODS Clinical data were collected to assess AGM’s incidence and identify the characteristics in 369 AP patients. In vitro, AP models were established using lipopolysaccharide in 266-6 acinar cells and MIN-6 β-cells. Cell proliferation, apoptosis, and protein expression were analyzed using the Cell Counting Kit-8 assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and western blotting. The TNF-α and insulin concentration in co-culture medium was measured by WJG [https://www.wjgnet.com](https://www.wjgnet.com) 1 December 21, 2025 Volume 31 Issue 47 Chen HF et al. TNF-α-induced β-cell apoptosis in AGM enzyme-linked immunosorbent assay. In vivo, an AP mouse model was induced using sodium taurocholate, and pancreatic tissues were analyzed through hematoxylin and eosin staining, terminal deoxynucleotidyl transferasedUTP nick-end labeling, and western blotting. TNF-α levels were assessed by enzyme-linked immunosorbent assay. A TNF-α inhibitor was applied to the AP cell model to reassess apoptosis and protein expression. RESULTS AGM occurred in 40.38% of AP patients. Body mass index, severity grade, recurrence frequency, and lung injury were significantly associated with AGM. AP models in 266-6 and MIN-6 cells showed reduced β-cell proliferation, insulin secretion, and increased apoptosis, which correlated with in

FAQs

What question does the study address about TNF-α and acute pancreatitis?

It examines TNF-α’s role in abnormal glucose metabolism after acute pancreatitis and how it affects islet β-cell apoptosis through molecular mechanisms.

How was abnormal glucose metabolism assessed in patients and models?

The study collected clinical data to determine AGM incidence and characteristics in 369 acute pancreatitis patients, and used cell and mouse models to evaluate β-cell function and apoptosis.

What molecular pathway links TNF-α to β-cell apoptosis in this work?

The findings implicate Bax/Bcl-2/caspase-3 signaling, with increased Bax and caspase-3 and decreased Bcl-2 after TNF-α elevation; TNF-α inhibition reverses these patterns.

Sep 28, 2026

Uploaded by Nguyễn Văn Học