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xenin-25(Gln) is a novel, chemically modified, enzymatically stable analogue of the gut peptide xenin-25. Developed by researchers at Ulster University, it is designed for the potential treatment of type 2 diabetes and obesity. Xenin-25 is a 25-amino acid peptide co-secreted with glucose-dependent insulinotropic polypeptide (GIP) from enteroendocrine K-cells. Native xenin-25 is rapidly degraded by plasma enzymes, limiting its therapeutic utility. In xenin-25(Gln), the naturally occurring lysine (Lys) and arginine (Arg) residues are substituted with glutamine (Gln) to prevent enzymatic cleavage, rendering the peptide resistant to plasma-mediated degradation for up to 24 hours. Preclinical studies demonstrate that xenin-25(Gln) exhibits improved glucose-lowering, insulinotropic, and satiety-inducing actions compared to the native peptide, and it synergistically enhances the insulin-releasing effects of GIP.
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