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

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.