Journal article

Publication year: 2020

Pages: 219-230

Journal: Journal of Endocrinology

Volume number: 245

Issue number: 2

ISSN: 0022-0795

Open access status: Green

DOI Link: https://doi.org/10.1530/JOE-19-0557

Publisher: BioScientifica

Abstract: 
Recent studies have characterised the biological properties and glucose-dependent insulinotropic polypeptide (GIP) potentiating actions of an enzymatically stable, C-terminal hexapeptide fragment of the gut hormone xenin, namely Psi-xenin-6. Given the primary therapeutic target of clinically approved dipeptidyl peptidase-4 (DPP-4) inhibitor drugs is augmentation of the incretin effect, the present study has assessed the capacity of Psi-xenin-6 to enhance the antidiabetic efficacy of sitagliptin in high fat fed (HFF) mice. Individual administration of either sitagliptin or Psi-xenin-6 alone for 18 days resulted in numerous metabolic benefits and positive effects on pancreatic islet architecture. As expected, sitagliptin therapy was associated with elevated circulating GIP and GLP-1 levels, with concurrent Psi-xenin-6 not elevating these hormones or enhancing DPP-4 inhibitory activity of the drug. However, combined sitagliptin and Psi-xenin-6 therapy in HFF mice was associated with further notable benefits, beyond that observed with either treatment alone. This included body weight change similar to lean controls, more pronounced and rapid benefits on circulating glucose and insulin as well as additional improvements in attenuating gluconeogenesis. Favourable effects on pancreatic islet architecture and peripheral insulin sensitivity were more apparent with combined therapy. Expression of hepatic genes involved in gluconeogenesis and insulin action were partially, or fully, restored to normal levels by the treatment regimens, with beneficial effects more prominent in the combination treatment group. These data demonstrate that combined treatment with Psi-xenin-6 and sitagliptin did not alter glucose tolerance but does offer some metabolic advantages, which merit further consideration as a therapeutic option for type 2 diabetes.

Harvard Citation style: Craig, S., Gault, V., Hamscher, G. and Irwin, N. (2020) Psi-Xenin-6 enhances sitagliptin effectiveness, but does not improve glucose tolerance, Journal of Endocrinology, 245(2), pp. 219-230. https://doi.org/10.1530/JOE-19-0557

APA Citation style: Craig, S., Gault, V., Hamscher, G., & Irwin, N. (2020). Psi-Xenin-6 enhances sitagliptin effectiveness, but does not improve glucose tolerance. Journal of Endocrinology. 245(2), 219-230. https://doi.org/10.1530/JOE-19-0557