Cadmium is known as an environmental pollutant that contributes to pancreatic damage and the pathogenesis of diabetes. However, less attention has been devoted to elucidating the mechanisms underlying Cd-induced pancreatic β-cell dysfunction and the role of Cd toxicity in the development of diabetes. In this study, we demonstrated that exposure to Cd caused remarkable pancreatic β-cell dysfunction and death, both in vitro and in vivo. Lipidomic analysis of Cd-exposed pancreatic β-cells using high-resolution mass spectrometry revealed that Cd exposure altered the profile and abundance of lipids. Cd exposure induced intracellular lipid accumulation, promoted lipid biogenesis, elevated pro-inflammatory lipid contents and inhibited lipid degradation. Furthermore, Cd exposure upregulated the expression levels of TNF-α, IL-1β and IL-6 in pancreatic β-cells and elevated the TNF-α, IL1-β and IL-6 levels in the serum and pancreas. Taken together, the results of our study demonstrated that environmental relevant Cd exposure causes pro-inflammatory lipids elevation and insulin secretion dysfunction in β-cells and hence exaggerates diabetes development. Combined exposure to environmental hazardous chemicals might markedly increase the probability of developing diabetes in humans. This study provides new metabolic and pharmacological targets for antagonizing Cd toxicity.

镉被认为是造成胰腺损害和糖尿病发病机理的环境污染物。但是，人们很少关注阐明Cd诱导的胰腺β细胞功能障碍的潜在机制以及Cd毒性在糖尿病发展中的作用。在这项研究中，我们证明了在体外和体内，暴露于Cd都会导致胰腺β细胞功能异常和死亡。。使用高分辨率质谱对暴露于镉的胰腺β细胞进行脂组学分析表明，暴露于镉改变了脂质的分布和丰度。镉暴露引起细胞内脂质积累，促进脂质生物发生，促炎性脂质含量升高并抑制脂质降解。此外，Cd暴露上调了胰腺β细胞中TNF-α，IL-1β和IL-6的表达水平，并升高了血清和胰腺中TNF-α，IL1-β和IL-6的水平。综上所述，我们的研究结果表明，与环境有关的镉暴露会导致β细胞中促炎性脂质升高和胰岛素分泌功能障碍，从而加剧糖尿病的发展。共同接触环境有害化学物质可能会显着增加人类患糖尿病的可能性。