Buha Aleksandra, Đukić-Ćosić Danijela, Ćurčić Marijana, Bulat Zorica, Antonijević Biljana, Moulis Jean-Marc, Goumenou Marina, Wallace David
Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade-Faculty of Pharmacy, 11000 Belgrade, Serbia.
Alternative Energies and Atomic Energy Commission-Fundamental Research Division-Interdisciplinary Research Institute of Grenoble (CEA-IRIG), University of Grenoble Alpes, F-38000 Grenoble, France.
Toxics. 2020 Aug 27;8(3):63. doi: 10.3390/toxics8030063.
Recent research has helped clarify the role of cadmium (Cd) in various pathological states. We have demonstrated Cd involvement in pancreatic cancer, as well as the bioaccumulation of Cd in the pancreas. Bioaccumulation and increased toxicity suggest that Cd may also be involved in other pancreas-mediated diseases, like diabetes. Cd falls into the category of "hyperglycemic" metals, i.e., metals that increase blood glucose levels, which could be due to increased gluconeogenesis, damage to β-cells leading to reduced insulin production, or insulin resistance at target tissue resulting in a lack of glucose uptake. This review addresses the current evidence for the role of Cd, leading to insulin resistance from human, animal, and in vitro studies. Available data have shown that Cd may affect normal insulin function through multiple pathways. There is evidence that Cd exposure results in the perturbation of the enzymes and modulatory proteins involved in insulin signal transduction at the target tissue and mutations of the insulin receptor. Cd, through well-described mechanisms of oxidative stress, inflammation, and mitochondrial damage, may also alter insulin production in β-cells. More work is necessary to elucidate the mechanisms associated with Cd-mediated insulin resistance.
近期研究有助于阐明镉（Cd）在各种病理状态中的作用。我们已经证实镉与胰腺癌有关，以及镉在胰腺中的生物蓄积。生物蓄积和毒性增加表明镉可能还与其他胰腺介导的疾病有关，如糖尿病。镉属于“升血糖”金属类别，即会升高血糖水平的金属，这可能是由于糖异生增加、β细胞受损导致胰岛素分泌减少，或靶组织胰岛素抵抗导致葡萄糖摄取不足。本综述阐述了来自人体、动物和体外研究的关于镉导致胰岛素抵抗作用的现有证据。现有数据表明，镉可能通过多种途径影响正常胰岛素功能。有证据表明，镉暴露会导致靶组织中参与胰岛素信号转导的酶和调节蛋白紊乱以及胰岛素受体突变。镉通过氧化应激、炎症和线粒体损伤等明确机制，也可能改变β细胞中的胰岛素分泌。需要开展更多工作来阐明与镉介导的胰岛素抵抗相关的机制。
