Biological Activity and Antidiabetic Potential of C-Terminal Octapeptide Fragments of the Gut-Derived Hormone Xenin

Journal article


Martin, Christine M., Parthsarathy, Vadivel, Hasib, Annie, NG, Ming T., McClean, Stephen, Flatt, Peter R., Gault, Victor A. and Irwin, Nigel 2016. Biological Activity and Antidiabetic Potential of C-Terminal Octapeptide Fragments of the Gut-Derived Hormone Xenin. PLos ONE. 11 (3). https://doi.org/10.1371/journal.pone.0152818
AuthorsMartin, Christine M., Parthsarathy, Vadivel, Hasib, Annie, NG, Ming T., McClean, Stephen, Flatt, Peter R., Gault, Victor A. and Irwin, Nigel
Abstract

Xenin is a peptide that is co-secreted with the incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), from intestinal K-cells in response to feeding. Studies demonstrate that xenin has appetite suppressive effects and modulates glucose-induced insulin secretion. The present study was undertaken to determine the bioactivity and antidiabetic properties of two C-terminal fragment xenin peptides, namely xenin 18-25 and xenin 18-25 Gln. In BRIN-BD11 cells, both xenin fragment peptides concentration-dependently stimulated insulin secretion, with similar efficacy as the parent peptide. Neither fragment peptide had any effect on acute feeding behaviour at elevated doses of 500 nmol/kg bw. When administered together with glucose to normal mice at 25 nmol/kg bw, the overall insulin secretory effect was significantly enhanced in both xenin 18-25 and xenin 18-25 Gln treated mice, with better moderation of blood glucose levels. Twice daily administration of xenin 18-25 or xenin 18-25 Gln for 21 days in high fat fed mice did not affect energy intake, body weight, circulating blood glucose or body fat stores. However, circulating plasma insulin concentrations had a tendency to be elevated, particularly in xenin 18-25 Gln mice. Both treatment regimens significantly improved insulin sensitivity by the end of the treatment period. In addition, sustained treatment with xenin 18-25 Gln significantly reduced the overall glycaemic excursion and augmented the insulinotropic response to an exogenous glucose challenge on day 21. In harmony with this, GIP-mediated glucose-lowering and insulin-releasing effects were substantially improved by twice daily xenin 18-25 Gln treatment. Overall, these data provide evidence that C-terminal octapeptide fragments of xenin, such as xenin 18-25 Gln, have potential therapeutic utility for type 2 diabetes.

Keywordsdiabetes; antihyperglycaemic; peptide fragments
Year2016
JournalPLos ONE
Journal citation11 (3)
PublisherPublic Library of Science (PLoS)
ISSN1932-6203
Digital Object Identifier (DOI)https://doi.org/10.1371/journal.pone.0152818
Web address (URL)http://hdl.handle.net/10545/622907
hdl:10545/622907
http://europepmc.org/article/med/27032106
Output statusPublished
Publication dates31 Mar 2016
Publication process dates
Deposited16 Aug 2018
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