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

Journal article


Martin, C.M., Parthsarathy, V., Pathak, V., Gault, V.A., Flatt, P.R. and Irwin, N. 2014. Characterisation of the biological activity of xenin-25 degradation fragment peptides. The Journal of Endocrinology. 221 (2), pp. 193-200. https://doi.org/10.1530/joe-13-0617
AuthorsMartin, C.M., Parthsarathy, V., Pathak, V., Gault, V.A., Flatt, P.R. and Irwin, N.
Abstract

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. In vitro studies using BRIN-BD11 cells demonstrated that native xenin-25 and xenin 18-25 possessed significant (P<0.05 to P<0.001) insulin-releasing actions at 5.6 and 16.7 mM glucose, respectively, but not at 1.1  mM glucose. In addition, xenin 18-25 significantly (P<0.05) potentiated the insulin-releasing action of the stable GIP mimetic (D-Ala²)GIP. In contrast, xenin 9-25, xenin 11-25 and xenin 14-25 displayed neither insulinotropic nor GIP-potentiating actions. Moreover, xenin 9-25, xenin 11-25 and xenin 14-25 significantly (P<0.05 to P<0.001) inhibited xenin-25 (10⁻⁶ M)-induced insulin release in vitro. I.p. administration of xenin-based peptides in combination with glucose to high fat-fed mice did not significantly affect the glycaemic excursion or glucose-induced insulin release compared with controls. However, when combined with (D-Ala²)GIP, all xenin peptides significantly (P<0.01 to P<0.001) reduced the overall glycaemic excursion, albeit to a similar extent as (D-Ala²)GIP alone. Xenin-25 and xenin 18-25 also imparted a potential synergistic effect on (D-Ala²)GIP-induced insulin release in high fat-fed mice. All xenin-based peptides lacked significant satiety effects in normal mice. These data demonstrate that the C-terminally derived fragment peptide of xenin-25, xenin 18-25, exhibits significant biological actions that could have therapeutic utility for obesity-diabetes.

Keywordsxenin-25; diabetes; insulin; obesity-diabetes
Year2014
JournalThe Journal of Endocrinology
Journal citation221 (2), pp. 193-200
Publisherbioscientifica
ISSN0022-0795
1479-6805
Digital Object Identifier (DOI)https://doi.org/10.1530/joe-13-0617
Web address (URL)http://europepmc.org/abstract/med/24520141
https://pure.ulster.ac.uk/en/publications/characterisation-of-the-biological-activity-of-xenin-25-degradati-3
Output statusPublished
Publication dates22 Apr 2014
Publication process dates
Deposited26 May 2022
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