The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist.

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist. / Thulesen, Jesper; Knudsen, Lotte Bjerre; Hartmann, Bolette; Hastrup, Sven; Kissow, Hannelouise; Jeppesen, Palle Bekker; Ørskov, Cathrine; Holst, Jens Juul; Poulsen, Steen Seier.

In: Regulatory Peptides, Vol. 103, No. 1, 2002, p. 9-15.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Thulesen, J, Knudsen, LB, Hartmann, B, Hastrup, S, Kissow, H, Jeppesen, PB, Ørskov, C, Holst, JJ & Poulsen, SS 2002, 'The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist.', Regulatory Peptides, vol. 103, no. 1, pp. 9-15.

APA

Thulesen, J., Knudsen, L. B., Hartmann, B., Hastrup, S., Kissow, H., Jeppesen, P. B., ... Poulsen, S. S. (2002). The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist. Regulatory Peptides, 103(1), 9-15.

Vancouver

Thulesen J, Knudsen LB, Hartmann B, Hastrup S, Kissow H, Jeppesen PB et al. The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist. Regulatory Peptides. 2002;103(1):9-15.

Author

Thulesen, Jesper ; Knudsen, Lotte Bjerre ; Hartmann, Bolette ; Hastrup, Sven ; Kissow, Hannelouise ; Jeppesen, Palle Bekker ; Ørskov, Cathrine ; Holst, Jens Juul ; Poulsen, Steen Seier. / The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist. In: Regulatory Peptides. 2002 ; Vol. 103, No. 1. pp. 9-15.

Bibtex

@article{c5cd0a80ab5211ddb5e9000ea68e967b,
title = "The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist.",
abstract = "The therapeutic potential of the intestinotrophic mediator glucagon-like peptide-2 (1-33) [GLP-2 (1-33)] has increased interest in the pharmacokinetics of the peptide. This study was undertaken to investigate whether the primary degradation product GLP-2 (3-33) interacts with the GLP-2 receptor. Functional (cAMP) and binding in vitro studies were carried out in cells expressing the transfected human GLP-2 receptor. Furthermore, a biologic response of GLP-2 (3-33) was tested in vivo. Mice were allocated to groups treated for 10 days (twice daily) with: (1) 5 microg GLP-2 (1-33), (2) 25 microg GLP-2 (3-33), (3) 5 microg GLP-2 (1-33)+100 microg GLP-2 (3-33), or (4) 5 microg GLP-2 (1-33)+500 microg GLP-2 (3-33). The intestine was investigated for growth changes. GLP-2 (3-33) bound to the GLP-2 receptor with a binding affinity of 7.5{\%} of that of GLP-2 (1-33). cAMP accumulation was stimulated with an efficacy of 15{\%} and a potency more than two orders of magnitude lower than that of GLP-2 (1-33). Increasing doses of GLP-2 (3-33) (10(-7)-10(-5) M) caused a shift to the right in the dose-response curve of GLP-2 (1-33). Treatment of mice with either GLP-2 (1-33) or (3-33) induced significant growth responses in both the small and large intestines, but the response induced by GLP-2 (3-33) was much smaller. Co-administration of 500 microg of GLP-2 (3-33) and 5 microg GLP-2 (1-33) resulted in a growth response that was smaller than that of 5 microg GLP-2 (1-33) alone. Consistent with the observed in vivo activities, our functional studies and binding data indicate that GLP-2 (3-33) acts as a partial agonist with potential competitive antagonistic properties on the GLP-2 receptor.",
author = "Jesper Thulesen and Knudsen, {Lotte Bjerre} and Bolette Hartmann and Sven Hastrup and Hannelouise Kissow and Jeppesen, {Palle Bekker} and Cathrine {\O}rskov and Holst, {Jens Juul} and Poulsen, {Steen Seier}",
note = "Keywords: Animals; Body Weight; Cell Line; Cricetinae; Cyclic AMP; Drug Administration Schedule; Female; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Humans; Image Processing, Computer-Assisted; Injections, Subcutaneous; Intestine, Large; Intestine, Small; Mice; Mice, Inbred C57BL; Organ Size; Peptide Fragments; Protein Binding; Random Allocation; Receptors, Glucagon; Recombinant Proteins; Transfection",
year = "2002",
language = "English",
volume = "103",
pages = "9--15",
journal = "Regulatory Peptides",
issn = "0167-0115",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist.

AU - Thulesen, Jesper

AU - Knudsen, Lotte Bjerre

AU - Hartmann, Bolette

AU - Hastrup, Sven

AU - Kissow, Hannelouise

AU - Jeppesen, Palle Bekker

AU - Ørskov, Cathrine

AU - Holst, Jens Juul

AU - Poulsen, Steen Seier

N1 - Keywords: Animals; Body Weight; Cell Line; Cricetinae; Cyclic AMP; Drug Administration Schedule; Female; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Humans; Image Processing, Computer-Assisted; Injections, Subcutaneous; Intestine, Large; Intestine, Small; Mice; Mice, Inbred C57BL; Organ Size; Peptide Fragments; Protein Binding; Random Allocation; Receptors, Glucagon; Recombinant Proteins; Transfection

PY - 2002

Y1 - 2002

N2 - The therapeutic potential of the intestinotrophic mediator glucagon-like peptide-2 (1-33) [GLP-2 (1-33)] has increased interest in the pharmacokinetics of the peptide. This study was undertaken to investigate whether the primary degradation product GLP-2 (3-33) interacts with the GLP-2 receptor. Functional (cAMP) and binding in vitro studies were carried out in cells expressing the transfected human GLP-2 receptor. Furthermore, a biologic response of GLP-2 (3-33) was tested in vivo. Mice were allocated to groups treated for 10 days (twice daily) with: (1) 5 microg GLP-2 (1-33), (2) 25 microg GLP-2 (3-33), (3) 5 microg GLP-2 (1-33)+100 microg GLP-2 (3-33), or (4) 5 microg GLP-2 (1-33)+500 microg GLP-2 (3-33). The intestine was investigated for growth changes. GLP-2 (3-33) bound to the GLP-2 receptor with a binding affinity of 7.5% of that of GLP-2 (1-33). cAMP accumulation was stimulated with an efficacy of 15% and a potency more than two orders of magnitude lower than that of GLP-2 (1-33). Increasing doses of GLP-2 (3-33) (10(-7)-10(-5) M) caused a shift to the right in the dose-response curve of GLP-2 (1-33). Treatment of mice with either GLP-2 (1-33) or (3-33) induced significant growth responses in both the small and large intestines, but the response induced by GLP-2 (3-33) was much smaller. Co-administration of 500 microg of GLP-2 (3-33) and 5 microg GLP-2 (1-33) resulted in a growth response that was smaller than that of 5 microg GLP-2 (1-33) alone. Consistent with the observed in vivo activities, our functional studies and binding data indicate that GLP-2 (3-33) acts as a partial agonist with potential competitive antagonistic properties on the GLP-2 receptor.

AB - The therapeutic potential of the intestinotrophic mediator glucagon-like peptide-2 (1-33) [GLP-2 (1-33)] has increased interest in the pharmacokinetics of the peptide. This study was undertaken to investigate whether the primary degradation product GLP-2 (3-33) interacts with the GLP-2 receptor. Functional (cAMP) and binding in vitro studies were carried out in cells expressing the transfected human GLP-2 receptor. Furthermore, a biologic response of GLP-2 (3-33) was tested in vivo. Mice were allocated to groups treated for 10 days (twice daily) with: (1) 5 microg GLP-2 (1-33), (2) 25 microg GLP-2 (3-33), (3) 5 microg GLP-2 (1-33)+100 microg GLP-2 (3-33), or (4) 5 microg GLP-2 (1-33)+500 microg GLP-2 (3-33). The intestine was investigated for growth changes. GLP-2 (3-33) bound to the GLP-2 receptor with a binding affinity of 7.5% of that of GLP-2 (1-33). cAMP accumulation was stimulated with an efficacy of 15% and a potency more than two orders of magnitude lower than that of GLP-2 (1-33). Increasing doses of GLP-2 (3-33) (10(-7)-10(-5) M) caused a shift to the right in the dose-response curve of GLP-2 (1-33). Treatment of mice with either GLP-2 (1-33) or (3-33) induced significant growth responses in both the small and large intestines, but the response induced by GLP-2 (3-33) was much smaller. Co-administration of 500 microg of GLP-2 (3-33) and 5 microg GLP-2 (1-33) resulted in a growth response that was smaller than that of 5 microg GLP-2 (1-33) alone. Consistent with the observed in vivo activities, our functional studies and binding data indicate that GLP-2 (3-33) acts as a partial agonist with potential competitive antagonistic properties on the GLP-2 receptor.

M3 - Journal article

VL - 103

SP - 9

EP - 15

JO - Regulatory Peptides

JF - Regulatory Peptides

SN - 0167-0115

IS - 1

ER -

ID: 8418400