Role of neddylation in diabetes metabolism: potential therapeutic target

Purpose: The study aimed to explore the role of neddylation in diabetes metabolism and its potential as a therapeutic target. Given the increasing global diabetes burden and limitations of current treatments, the research question was to determine how neddylation affects diabetes pathophysiology and if targeting it could offer new treatment strategies. Methods: The authors gathered data from a comprehensive review of existing research on neddylation in diabetes, including studies on insulin signaling, glucose and lipid metabolism, and related diseases. Experimental models, including diabetic mice and granulosa cells, and pharmacological interventions like MLN4924 were also thoroughly reviewed. By collating and evaluating these sources of information, the authors analyzed the influence of neddylation on diverse molecules and pathways implicated in diabetes. Results: Neddylation is involved in multiple aspects of diabetes. It affects insulin signaling by modifying insulin receptor substrate (IRS), inositol hexakisphosphate (IP6), phosphoenolpyruvate carboxykinase 1 (PCK1), and other molecules. Inhibiting neddylation with drugs like MLN4924 can reduce hepatic glucose generation, alleviate hyperglycemia, and improve metabolic phenotypes in mouse models. Neddylation is also associated with related diseases such as familial hyperkalemic hypertension, obesity - related metabolic disorders, and nonalcoholic steatohepatitis combined with type 2 diabetes. Conclusion: Neddylation plays a significant role in glucose metabolism regulation and diabetes pathogenesis. Targeting neddylation, especially with inhibitors like MLN4924, shows promise as a new therapeutic strategy for diabetes. Further research on neddylation in diabetes is needed to solidify its potential in treatment and management.