RNA-binding proteins (RBPs) lie at the center of posttranscriptional regulation and the\ndysregulation of RBPs contributes to diabetes. Therefore, the modulation of RBPs is anticipated\nto become a potential therapeutic approach to diabetes. CYC27 is a synthetic derivative of marine\nbromophenol BDB, which is isolated from red alga Rhodomela confervoides. In this study, we found\nthat CYC27 significantly lowered the blood glucose levels of diabetic BKS db mice. Moreover, CYC27\neffectively ameliorated dyslipidemia in BKS db mice by reducing their total serum cholesterol (TC)\nand triglyceride (TG) levels. Furthermore, CYC27 was an insulin-sensitizing agent with increased\ninsulin-stimulated phosphorylation of insulin receptors and relevant downstream factors. Finally, to\nsystemically study the mechanisms of CYC27, label-free quantitative phosphoproteomic analysis was\nperformed to investigate global changes in phosphorylation. Enriched GO annotation showed that\nmost regulated phosphoproteins were related to RNA splicing and RNA processing. Enriched KEGG\nanalysis showed that a spliceosome-associated pathway was the predominant pathway after CYC27\ntreatment. Protein-protein interaction (PPI) analysis showed that CYC27 modulated the process of\nmRNA splicing via phosphorylation of the relevant RBPs, including upregulated Cstf3 and Srrt. Our\nresults suggested that CYC27 treatment exerted promising anti-diabetic effects by sensitizing the\ninsulin signaling pathways and modulating RNA splicing-associated RBPs.
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