Chronic exposure to incretin metabolites GLP-1(9-36) and GIP(3-42) affect islet morphology and beta cell health in high fat fed mice

Ananyaa Sridhar, Dawood Khan, Gayathri Babu, Nigel Irwin, Victor A Gault, Peter R Flatt, Charlotte R Moffett

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Abstract

The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are rapidly degraded by dipeptidyl peptidase-4 (DPP-4) to their major circulating metabolites GLP-1(9-36) and GIP(3-42). This study investigates the possible effects of these metabolites, and the equivalent exendin molecule Ex(9-39), on pancreatic islet morphology and constituent alpha and beta cells in high-fat diet (HFD) fed mice. Male Swiss TO-mice (6-8 weeks-old) were maintained on a HFD or normal diet (ND) for 4 months and then received twice-daily subcutaneous injections of GLP-1(9-36), GIP(3-42), Ex(9-39) (25 nmol/kg bw) or saline vehicle (0.9% (w/v) NaCl) over a 60-day period. Metabolic parameters were monitored and excised pancreatic tissues were used for immunohistochemical analysis. Body weight and assessed metabolic indices were not changed by peptide administration. GLP-1(9-36) significantly (p
Original languageEnglish
Article number171254
Pages (from-to)1-8
Number of pages8
JournalPeptides
Volume178
Early online date28 May 2024
DOIs
Publication statusPublished online - 28 May 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Data Access Statement

Data will be made available on request.

Keywords

  • Islets
  • Incretin
  • GIP(3−42)
  • GLP-1(9−36)

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