Diabetes-related complications are becoming increasingly common as the global prevalence of diabetes increases. Diabetes is also linked to a high risk of developing cancer. This raises the question of whether cancer vulnerability is caused by diabetes itself or the use of antidiabetic drugs. Chromosomal instability, a source of genetic modification involving either an altered chromosomal number or structure, is a hallmark of cancer. Saxagliptin has been approved by the FDA for diabetes treatment. However, the detailed in vivo effects of prolonged saxagliptin treatment on chromosomal instability have not yet been reported. In this study, streptozotocin was used to induce diabetes in mice, and both diabetic and non-diabetic mice received saxagliptin for five weeks. Fluorescence in situ hybridization was conducted in combination with a bone marrow micronucleus test for measuring chromosomal instability. Our results indicated that saxagliptin is neither mutagenic nor cytotoxic, under the given treatment regimen. Diabetic mice had a much higher incidence of micronuclei formation, and a centromeric DNA probe was present inside the majority of the induced micronuclei, indicating that most of these were caused by chromosome nondisjunction. Conversely, diabetic mice treated with saxagliptin exhibited a significant decrease in micronuclei induction, which were centromeric-positive and centromeric-negative. Diabetes also causes significant biochemical changes indicative of oxidative stress, such as increased lipid peroxidation and decreased reduced/oxidized glutathione ratio, which was reversed by saxagliptin administration. Overall, saxagliptin, the non-mutagenic antidiabetic drug, maintains chromosomal integrity in diabetes and reduces micronuclei formation by restoring redox imbalance, further indicating its usefulness in diabetic patients.

随着全球糖尿病患病率的增加，与糖尿病相关的并发症变得越来越常见。糖尿病还与患癌症的高风险有关。这就提出了一个问题：癌症易感性是由糖尿病本身引起的还是由抗糖尿病药物的使用引起的。染色体不稳定性是涉及染色体数量或结构改变的基因修饰的根源，是癌症的一个标志。沙格列汀已被 FDA 批准用于糖尿病治疗。然而，长期沙格列汀治疗对染色体不稳定性的详细体内影响尚未报道。在这项研究中，链脲佐菌素被用来诱导小鼠患糖尿病，糖尿病小鼠和非糖尿病小鼠均接受沙格列汀治疗五周。荧光原位杂交与骨髓微核测试结合进行，以测量染色体不稳定性。我们的结果表明，在给定的治疗方案下，沙格列汀既不具有诱变性，也不具有细胞毒性。糖尿病小鼠微核形成的发生率要高得多，并且大多数诱导的微核内存在着丝粒DNA探针，这表明其中大部分是由染色体不分离引起的。相反，用沙格列汀治疗的糖尿病小鼠表现出着丝粒阳性和着丝粒阴性微核诱导显着减少。糖尿病还会引起表明氧化应激的显着生化变化，例如脂质过氧化增加和还原型/氧化型谷胱甘肽比率降低，而沙格列汀可以逆转这种变化。总体而言，沙格列汀是一种非诱变抗糖尿病药物，可维持糖尿病患者的染色体完整性，并通过恢复氧化还原失衡来减少微核形成，进一步表明其在糖尿病患者中的有用性。