Glucagon-like peptide-1 (GLP-1) receptor agonism or DPP-4 inhibition does not accelerate neoplasia in carcinogen treated mice

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Hannelouise Kissow, Bolette Hartmann, Jens Juul Holst, Niels-Erik Viby, Lærke Schmidt Hansen, Mette Marie Rosenkilde, Kristine Juul Hare, Steen Seier Poulsen

Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are secreted in parallel from the intestinal endocrine cells after nutrient intake. GLP-1 is an incretin hormone and analogues are available for the treatment of type 2 diabetes mellitus (T2DM). GLP-2 is an intestinal growth hormone and is shown to promote growth of colonic adenomas in carcinogen treated mice. Both peptides are degraded by dipeptidyl peptidase-4 (DPP-4) into inactive metabolites. DPP-4 inhibitors are therefore also in use for treatment of T2DM. It is possible that DPP-4 inhibition by enhancing the exposure of endogenous GLP-2 to the intestinal epithelia also might mediate growth and promote neoplasia. We investigated the intestinal growth effect of the GLP-1 receptor agonists (GLP-1 RAs) (liraglutide and exenatide) and DPP-4 inhibition (sitagliptin) in healthy mice. We also investigated the potential tumour promoting effect of liraglutide and sitaglitin in the colon of carcinogen treated mice. We used GLP-2 as a positive control.
Original languageEnglish
JournalRegulatory Peptides
Volume179
Issue number1-3
Pages (from-to)91-100
Number of pages10
ISSN0167-0115
DOIs
Publication statusPublished - 10 Nov 2012

    Research areas

  • 1,2-Dimethylhydrazine, Aberrant Crypt Foci, Adenoma, Anatomy, Cross-Sectional, Animals, COS Cells, Cercopithecus aethiops, Colon, Colonic Neoplasms, Cyclic AMP, Diabetes Mellitus, Type 2, Dipeptidyl Peptidase 4, Dipeptidyl-Peptidase IV Inhibitors, Female, Glucagon-Like Peptide 1, Hypoglycemic Agents, Intestinal Mucosa, Intestine, Small, Mice, Mice, Inbred C57BL, Organ Size, Peptides, Pyrazines, Receptors, Glucagon, Transfection, Triazoles, Venoms

ID: 45041252