Single-Atom Ce-N_(4)-C-(OH)_(2)Nanozyme-Catalyzed Cascade Reaction to Alleviate Hyperglycemia

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_(4)-C-(OH)_(2)(SACe-N_(4)-C-(OH)_(2))nanozyme promoted glucose absorption in lysosomes,resulting in increased reactive oxygen species production in HepG2 cells.Furthermore,the SACe-N_(4)-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 SACeN_(4)-C-(OH)_(2)alleviated the effects of hyperglycemia without evident toxicity,demonstrating its excellent clinical application potential.