Characterisation of the biological activity of xenin-25 degradation fragment peptides
Journal article
Authors | Martin, C.M., Parthsarathy, V., Pathak, V., Gault, V.A., Flatt, P.R. and Irwin, N. |
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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. |
Keywords | xenin-25; diabetes; insulin; obesity-diabetes |
Year | 2014 |
Journal | The Journal of Endocrinology |
Journal citation | 221 (2), pp. 193-200 |
Publisher | bioscientifica |
ISSN | 0022-0795 |
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 status | Published |
Publication dates | 22 Apr 2014 |
Publication process dates | |
Deposited | 26 May 2022 |
https://repository.derby.ac.uk/item/96yvz/characterisation-of-the-biological-activity-of-xenin-25-degradation-fragment-peptides
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