Antimony induces oxidative stress to impair enteroendocrine cells and disrupt glucose homeostasis

  • J Hazard Mater. 2025 Nov 25:501:140617. doi: 10.1016/j.jhazmat.2025.140617.
Lanfei Jin  1 ,  Longtao Zhu  2 ,  Chengdong Wu  3 ,  Weiqiong Jin  2 ,  Ke Liu  2 ,  Junxuan Peng  4 ,  Xin Xu  4 ,  Xiaolong Ge  4 ,  Ying Zhu  2 ,  Xiaole Sheng  5 ,  Rongpan Bai  6 ,  Guangdi Chen  7
Affiliations
  • 1. Department of General Surgery, Sir Run Run Shaw Hospital and Institute of Environmental Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, China; Zhejiang Key Laboratory of Precise Diagnosis and Treatment of Abdominal Infection, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
  • 2. Department of Public Health, and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
  • 3. Department of Thyroid Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310020, China.
  • 4. Department of General Surgery, Sir Run Run Shaw Hospital and Institute of Environmental Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, China.
  • 5. Department of General Surgery, Sir Run Run Shaw Hospital and Institute of Environmental Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, China; Zhejiang Key Laboratory of Precise Diagnosis and Treatment of Abdominal Infection, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China. Electronic address: [email protected].
  • 6. Department of General Surgery, Sir Run Run Shaw Hospital and Institute of Environmental Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, China; Zhejiang Key Laboratory of Precise Diagnosis and Treatment of Abdominal Infection, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China. Electronic address: [email protected].
  • 7. Department of Public Health, and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China. Electronic address: [email protected].
PMID: 41337963 DOI: 10.1016/j.jhazmat.2025.140617
Abstract

Enteroendocrine L and K cells play pivotal roles in glucose homeostasis through producing the key intestinal Hormones GLP-1 and GIP, respectively. Antimony (Sb) exposure has been associated with an elevated risk of diabetes, but the molecular mechanisms involved remain poorly understood. In this study, we identified a significant inverse correlation between urinary Sb levels and clinical glycemic markers. We further demonstrated that Sb exposure impairs the function of enteroendocrine L and K cells, leading to reduced production of GLP-1 and GIP, thereby disrupting systemic glucose regulation. Mechanistically, Sb-induced oxidative stress modulates crucial signaling pathways, inhibiting GLP-1 expression and suppressing GIP expression via downregulation of essential transcription factors. These findings provide novel insights into the pathogenic link between environmental Sb exposure and metabolic dysfunction, offering a mechanistic basis for epidemiological associations of Sb with diabetes.

Keywords
Antimony; Enteroendocrine cells; Glucose homeostasis; Oxidative stress.
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