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

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

doi:10.1016/j.regpep.2012.08.016

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

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

Research output: Contribution to journal › Journal article › Research › peer-review

87 Citations (Scopus)

Abstract

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 language	English
Journal	Regulatory Peptides
Volume	179
Issue number	1-3
Pages (from-to)	91-100
Number of pages	10
ISSN	0167-0115
DOIs	https://doi.org/10.1016/j.regpep.2012.08.016
Publication status	Published - 10 Nov 2012

Keywords

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

Access to Document

10.1016/j.regpep.2012.08.016

Cite this

Glucagon-like peptide-1 (GLP-1) receptor agonism or DPP-4 inhibition does not accelerate neoplasia in carcinogen treated mice. / Kissow, Hannelouise ; Hartmann, Bolette ; Holst, Jens Juul; Viby, Niels-Erik; Hansen, Lærke Schmidt ; Rosenkilde, Mette Marie; Hare, Kristine Juul; Poulsen, Steen Seier.

In: Regulatory Peptides, Vol. 179, No. 1-3, 10.11.2012, p. 91-100.

Research output: Contribution to journal › Journal article › Research › peer-review

Kissow, Hannelouise ; Hartmann, Bolette ; Holst, Jens Juul ; Viby, Niels-Erik ; Hansen, Lærke Schmidt ; Rosenkilde, Mette Marie ; Hare, Kristine Juul ; Poulsen, Steen Seier. / Glucagon-like peptide-1 (GLP-1) receptor agonism or DPP-4 inhibition does not accelerate neoplasia in carcinogen treated mice. In: Regulatory Peptides. 2012 ; Vol. 179, No. 1-3. pp. 91-100.

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abstract = "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.",

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T1 - Glucagon-like peptide-1 (GLP-1) receptor agonism or DPP-4 inhibition does not accelerate neoplasia in carcinogen treated mice

AU - Kissow, Hannelouise

AU - Hartmann, Bolette

AU - Holst, Jens Juul

AU - Viby, Niels-Erik

AU - Hansen, Lærke Schmidt

AU - Rosenkilde, Mette Marie

AU - Hare, Kristine Juul

AU - Poulsen, Steen Seier

PY - 2012/11/10

Y1 - 2012/11/10

N2 - 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.

AB - 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.

KW - 1,2-Dimethylhydrazine

KW - Aberrant Crypt Foci

KW - Adenoma

KW - Anatomy, Cross-Sectional

KW - Animals

KW - COS Cells

KW - Cercopithecus aethiops

KW - Colon

KW - Colonic Neoplasms

KW - Cyclic AMP

KW - Diabetes Mellitus, Type 2

KW - Dipeptidyl Peptidase 4

KW - Dipeptidyl-Peptidase IV Inhibitors

KW - Female

KW - Glucagon-Like Peptide 1

KW - Hypoglycemic Agents

KW - Intestinal Mucosa

KW - Intestine, Small

KW - Mice

KW - Mice, Inbred C57BL

KW - Organ Size

KW - Peptides

KW - Pyrazines

KW - Receptors, Glucagon

KW - Transfection

KW - Triazoles

KW - Venoms

U2 - 10.1016/j.regpep.2012.08.016

DO - 10.1016/j.regpep.2012.08.016

M3 - Journal article

C2 - 22989472

VL - 179

SP - 91

EP - 100

JO - Regulatory Peptides

JF - Regulatory Peptides

SN - 0167-0115

IS - 1-3

ER -