Song Guangchun, Xu Jia, Zhong Hong, Zhang Qi, Wang Xin, Lin Yitong, Beckman Scott P, Luo Yunbo, He Xiaoyun, Li Jin-Cheng, Huang Kunlun, Cheng Nan
Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164, USA.
Research (Wash D C). 2023;6:0095. doi: 10.34133/research.0095. Epub 2023 Mar 30.
The enzyme-mimicking catalytic activity of single-atom nanozymes has been widely used in tumor treatment. However, research on alleviating metabolic diseases, such as hyperglycemia, has not been reported. Herein, we found that the single-atom Ce-N-C-(OH) (SACe-N-C-(OH)) nanozyme promoted glucose absorption in lysosomes, resulting in increased reactive oxygen species production in HepG2 cells. Furthermore, the SACe-N-C-(OH) nanozyme initiated a cascade reaction involving superoxide dismutase-, oxidase-, catalase-, and peroxidase-like activity to overcome the limitations associated with the substrate and produce •OH, thus improving glucose intolerance and insulin resistance by increasing the phosphorylation of protein kinase B and glycogen synthase kinase 3β, and the expression of glycogen synthase, promoting glycogen synthesis to improve glucose intolerance and insulin resistance in high-fat diet-induced hyperglycemic mice. Altogether, these results demonstrated that the novel nanozyme SACe-N-C-(OH) alleviated the effects of hyperglycemia without evident toxicity, demonstrating its excellent clinical application potential.
单原子纳米酶的模拟酶催化活性已广泛应用于肿瘤治疗。然而，关于缓解高血糖等代谢疾病的研究尚未见报道。在此，我们发现单原子Ce-N-C-(OH)（SACe-N-C-(OH)）纳米酶促进溶酶体对葡萄糖的吸收，导致HepG2细胞中活性氧生成增加。此外，SACe-N-C-(OH)纳米酶引发了一系列涉及超氧化物歧化酶、氧化酶、过氧化氢酶和过氧化物酶样活性的级联反应，以克服与底物相关的限制并产生•OH，从而通过增加蛋白激酶B和糖原合酶激酶3β的磷酸化以及糖原合酶的表达来改善葡萄糖不耐受和胰岛素抵抗，促进糖原合成以改善高脂饮食诱导的高血糖小鼠的葡萄糖不耐受和胰岛素抵抗。总之，这些结果表明新型纳米酶SACe-N-C-(OH)可缓解高血糖的影响且无明显毒性，显示出其优异的临床应用潜力。
