GIP-Xenin hybrid peptide

GIP-Xenin hybrid peptide (GIP-XEN) is a chemically modified, enzymatically stable hybrid peptide designed for the treatment of type 2 diabetes mellitus and obesity. It was engineered by linking amino acid residues 1-14 of glucose-dependent insulinotropic polypeptide (GIP) with residues 18-25 of xenin (xenin-8). To enhance stability against dipeptidyl peptidase-4 (DPP4) degradation, L-alanine at position 2 of the GIP sequence was substituted with D-alanine, and lysine and arginine residues at positions 21 and 22 of xenin-8 were substituted with glutamine. GIP-XEN acts as a dual agonist targeting both the GIP receptor and neurotensin receptor 1 (NTSR1), combining the insulinotropic effects of GIP with the satiety-inducing and GIP-potentiating actions of xenin. Preclinical studies in high-fat-fed mice have demonstrated that GIP-XEN improves glucose tolerance, restores GIP sensitivity, enhances beta-cell function, and reduces food intake.

Other names

(DAla2)GIP/xenin-8-GlnGIP/xenin hybrid peptide