单原子纳米酶（nanozyme）具有类酶催化活性，已被广泛应用于肿瘤治疗。然而，有关缓解代谢疾病如高血糖等方面的研究尚未报道。在此，我们发现单原子Ce-N4-C-(OH)2（SACe-N4-C-(OH)2）纳米酶促进了溶酶体中的葡萄糖吸收，导致HepG2细胞中反应性氧（ROS）的产生增加。此外，SACe-N4-C-(OH)2纳米酶引发了一个级联反应，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，以克服底物的限制并产生•OH，从而通过增加蛋白激酶B和糖原合成酶3β的磷酸化，以及糖原合成酶的表达促进糖原合成，在高脂饮食诱导的高血糖小鼠中改善葡萄糖不耐受和胰岛素抵抗。这些结果共同证明了新型纳米酶SACe-N4-C-(OH)2具有无明显毒性的优秀临床应用潜力，有助于缓解高血糖的影响。

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-N4-C-(OH)2 (SACe-N4-C-(OH)2) nanozyme promoted glucose absorption in lysosomes, resulting in increased reactive oxygen species production in HepG2 cells. Furthermore, the SACe-N4-C-(OH)2 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-N4-C-(OH)2 alleviated the effects of hyperglycemia without evident toxicity, demonstrating its excellent clinical application potential.