GLP-1 receptor agonism and GIP receptor antagonism induce substantial alterations in enteroendocrine and islet cell populations in obese high fat fed mice

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
21 Downloads (Pure)

Abstract

Effects of sustained activation of glucagon-like peptide-1 (GLP-1) receptors (GLP-1R) as well as antagonism of receptors for glucose-dependent insulinotropic peptide (GIP) on intestinal morphology and related gut hormone populations have not been fully investigated. The present study assesses the impact of 21-days twice daily treatment with the GLP-1R agonist exendin-4 (Ex-4), or the GIP receptor (GIPR) antagonist mGIP(3-30), on these features in obese mice fed a high fat diet (HFD). HFD mice presented with reduced crypt depth when compared to normal diet (ND) controls, which was reversed by Ex-4 treatment. Both regimens lead to an enlargement of villi length in HFD mice. HFD mice had increased numbers of GIP and PYY positive ileal cells, with both treatment interventions reversing the effect on PYY positive cells, but only Ex-4 restoring GIP ileal cell populations to ND levels. Ex-4 and mGIP (3-30) marginally decreased GLP-1 villi immunoreactivity and countered the reduction of ileal GLP-1 content caused by HFD. As expected, HFD mice presented with elevated pancreatic islet area. Interestingly, mGIP(3-30), but not Ex-4, enhanced islet and beta-cell areas in HFD mice despite lack of effect of beta-cell turnover, whilst Ex-4 increased delta-cell area. Co-localisation of islet PYY or GLP-1 with glucagon was increased by Ex-4, whilst islet PYY co-immunoreactivity with somatostatin was enhanced by mGIP(3-30) treatment. These observations highlight potential new mechanisms linked to the metabolic benefits of GLP-1R agonism and GIPR antagonism in obesity.

Original languageEnglish
Article number171093
Pages (from-to)1-9
Number of pages9
JournalPeptides
Volume169
Early online date1 Sept 2023
DOIs
Publication statusPublished (in print/issue) - 30 Nov 2023

Bibliographical note

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Funding Information:
These studies were supported by Diabetes UK RD Lawrence Fellowship grant to RCM and Ulster University strategic funding.

Publisher Copyright:
© 2023 The Authors

Keywords

  • Enteroendocrine cell
  • GIP
  • GLP-1
  • High fat diet (HFD)
  • Incretin
  • Islet
  • PYY

Fingerprint

Dive into the research topics of 'GLP-1 receptor agonism and GIP receptor antagonism induce substantial alterations in enteroendocrine and islet cell populations in obese high fat fed mice'. Together they form a unique fingerprint.

Cite this