Characterisation of the biological activity of xenin-25 degradation fragment peptides.

Xenin-25, a peptide co-secreted with the incretin hormone glucose-dependent insulinotropic polypeptide (GIP), possesses promising therapeutic actions for obesity-diabetes. However, native xenin-25 is rapidly degraded by serum enzymes to yield the truncated metabolites: xenin 9-25, xenin 11-25, xenin 14-25 and xenin 18-25. This study has examined the biological activities of these fragment peptides.

A novel acylated form of (d-Ala(2))GIP with improved antidiabetic potential, lacking effect on body fat stores.

Background: Rapid enzymatic degradation of the incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), limits therapeutic use of the native peptide for diabetes. However, enzymatically stable analogues of GIP, such as (d-Ala(2))GIP, have been generated, but are still susceptible to renal filtration.

Methods: The present study examines the in vitro and in vivo biological actions of a novel, acylated GIP analogue, (d-Ala(2))GIP[Lys(37)PAL].

Degradation, insulin secretion, glucose-lowering and GIP additive actions of a palmitate-derivatised analogue of xenin-25.

Xenin-25, a K-cell derived peptide co-secreted with glucose-dependent insulinotropic polypeptide (GIP), has recently been shown to have glucose homeostatic actions and potentiate the insulinotropic effect of GIP. However, the biological actions of xenin-25 are brief due to rapid metabolism, yet little is known regarding enzymatic degradation of this peptide. Therefore, the present study has fully characterised the plasma enzymatic degradation products of xenin-25.