Glucose-dependent insulinotropic polypeptide receptor antagonist treatment causes a reduction in weight gain in ovariectomised high fat diet-fed mice

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Standard

Glucose-dependent insulinotropic polypeptide receptor antagonist treatment causes a reduction in weight gain in ovariectomised high fat diet-fed mice. / Boer, Geke Aline; Hunt, Jenna Elizabeth; Gabe, Maria Buur Nordskov; Windeløv, Johanne Agerlin; Sparre-Ulrich, Alexander Hovard; Hartmann, Bolette; Holst, Jens Juul; Rosenkilde, Mette Marie.

I: British Journal of Pharmacology, Bind 179, Nr. 18, 2022, s. 4486-4499.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Boer, GA, Hunt, JE, Gabe, MBN, Windeløv, JA, Sparre-Ulrich, AH, Hartmann, B, Holst, JJ & Rosenkilde, MM 2022, 'Glucose-dependent insulinotropic polypeptide receptor antagonist treatment causes a reduction in weight gain in ovariectomised high fat diet-fed mice', British Journal of Pharmacology, bind 179, nr. 18, s. 4486-4499. https://doi.org/10.1111/bph.15894

APA

Boer, G. A., Hunt, J. E., Gabe, M. B. N., Windeløv, J. A., Sparre-Ulrich, A. H., Hartmann, B., Holst, J. J., & Rosenkilde, M. M. (2022). Glucose-dependent insulinotropic polypeptide receptor antagonist treatment causes a reduction in weight gain in ovariectomised high fat diet-fed mice. British Journal of Pharmacology, 179(18), 4486-4499. https://doi.org/10.1111/bph.15894

Vancouver

Boer GA, Hunt JE, Gabe MBN, Windeløv JA, Sparre-Ulrich AH, Hartmann B o.a. Glucose-dependent insulinotropic polypeptide receptor antagonist treatment causes a reduction in weight gain in ovariectomised high fat diet-fed mice. British Journal of Pharmacology. 2022;179(18):4486-4499. https://doi.org/10.1111/bph.15894

Author

Boer, Geke Aline ; Hunt, Jenna Elizabeth ; Gabe, Maria Buur Nordskov ; Windeløv, Johanne Agerlin ; Sparre-Ulrich, Alexander Hovard ; Hartmann, Bolette ; Holst, Jens Juul ; Rosenkilde, Mette Marie. / Glucose-dependent insulinotropic polypeptide receptor antagonist treatment causes a reduction in weight gain in ovariectomised high fat diet-fed mice. I: British Journal of Pharmacology. 2022 ; Bind 179, Nr. 18. s. 4486-4499.

Bibtex

@article{4d1756d4bf934cfba5a770f93fb9af15,
title = "Glucose-dependent insulinotropic polypeptide receptor antagonist treatment causes a reduction in weight gain in ovariectomised high fat diet-fed mice",
abstract = "BACKGROUND AND PURPOSE: The incretin hormone, gastric inhibitory peptide/glucose-dependent insulinotropic polypeptide (GIP), secreted by the enteroendocrine K-cells in the proximal intestine, may regulate lipid metabolism and adiposity, but its exact role in these processes is unclear.EXPERIMENTAL APPROACH: We characterized in vitro and in vivo antagonistic properties of a novel GIP analogue, mGIPAnt-1. We further assessed the in vivo pharmacokinetic profile of this antagonist, as well as its ability to affect high-fat diet (HFD)-induced body weight gain in ovariectomised mice during an 8-week treatment period.KEY RESULTS: mGIPAnt-1 showed competitive antagonistic properties to the GIP receptor in vitro as it inhibited GIP-induced cAMP accumulation in COS-7 cells. Furthermore, mGIPAnt-1 was capable of inhibiting GIP-induced glucoregulatory and insulinotropic effects in vivo and has a favourable pharmacokinetic profile with a half-life of 7.2 h in C57Bl6 female mice. Finally, sub-chronic treatment with mGIPAnt-1 in ovariectomised HFD mice resulted in a reduction of body weight and fat mass.CONCLUSION AND IMPLICATIONS: mGIPAnt-1 successfully inhibited acute GIP-induced effects in vitro and in vivo and sub-chronically induces resistance to HFD-induced weight gain in ovariectomised mice. Our results support the development of GIP antagonists for the therapy of obesity.",
author = "Boer, {Geke Aline} and Hunt, {Jenna Elizabeth} and Gabe, {Maria Buur Nordskov} and Windel{\o}v, {Johanne Agerlin} and Sparre-Ulrich, {Alexander Hovard} and Bolette Hartmann and Holst, {Jens Juul} and Rosenkilde, {Mette Marie}",
note = "{\textcopyright} 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.",
year = "2022",
doi = "10.1111/bph.15894",
language = "English",
volume = "179",
pages = "4486--4499",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley",
number = "18",

}

RIS

TY - JOUR

T1 - Glucose-dependent insulinotropic polypeptide receptor antagonist treatment causes a reduction in weight gain in ovariectomised high fat diet-fed mice

AU - Boer, Geke Aline

AU - Hunt, Jenna Elizabeth

AU - Gabe, Maria Buur Nordskov

AU - Windeløv, Johanne Agerlin

AU - Sparre-Ulrich, Alexander Hovard

AU - Hartmann, Bolette

AU - Holst, Jens Juul

AU - Rosenkilde, Mette Marie

N1 - © 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

PY - 2022

Y1 - 2022

N2 - BACKGROUND AND PURPOSE: The incretin hormone, gastric inhibitory peptide/glucose-dependent insulinotropic polypeptide (GIP), secreted by the enteroendocrine K-cells in the proximal intestine, may regulate lipid metabolism and adiposity, but its exact role in these processes is unclear.EXPERIMENTAL APPROACH: We characterized in vitro and in vivo antagonistic properties of a novel GIP analogue, mGIPAnt-1. We further assessed the in vivo pharmacokinetic profile of this antagonist, as well as its ability to affect high-fat diet (HFD)-induced body weight gain in ovariectomised mice during an 8-week treatment period.KEY RESULTS: mGIPAnt-1 showed competitive antagonistic properties to the GIP receptor in vitro as it inhibited GIP-induced cAMP accumulation in COS-7 cells. Furthermore, mGIPAnt-1 was capable of inhibiting GIP-induced glucoregulatory and insulinotropic effects in vivo and has a favourable pharmacokinetic profile with a half-life of 7.2 h in C57Bl6 female mice. Finally, sub-chronic treatment with mGIPAnt-1 in ovariectomised HFD mice resulted in a reduction of body weight and fat mass.CONCLUSION AND IMPLICATIONS: mGIPAnt-1 successfully inhibited acute GIP-induced effects in vitro and in vivo and sub-chronically induces resistance to HFD-induced weight gain in ovariectomised mice. Our results support the development of GIP antagonists for the therapy of obesity.

AB - BACKGROUND AND PURPOSE: The incretin hormone, gastric inhibitory peptide/glucose-dependent insulinotropic polypeptide (GIP), secreted by the enteroendocrine K-cells in the proximal intestine, may regulate lipid metabolism and adiposity, but its exact role in these processes is unclear.EXPERIMENTAL APPROACH: We characterized in vitro and in vivo antagonistic properties of a novel GIP analogue, mGIPAnt-1. We further assessed the in vivo pharmacokinetic profile of this antagonist, as well as its ability to affect high-fat diet (HFD)-induced body weight gain in ovariectomised mice during an 8-week treatment period.KEY RESULTS: mGIPAnt-1 showed competitive antagonistic properties to the GIP receptor in vitro as it inhibited GIP-induced cAMP accumulation in COS-7 cells. Furthermore, mGIPAnt-1 was capable of inhibiting GIP-induced glucoregulatory and insulinotropic effects in vivo and has a favourable pharmacokinetic profile with a half-life of 7.2 h in C57Bl6 female mice. Finally, sub-chronic treatment with mGIPAnt-1 in ovariectomised HFD mice resulted in a reduction of body weight and fat mass.CONCLUSION AND IMPLICATIONS: mGIPAnt-1 successfully inhibited acute GIP-induced effects in vitro and in vivo and sub-chronically induces resistance to HFD-induced weight gain in ovariectomised mice. Our results support the development of GIP antagonists for the therapy of obesity.

U2 - 10.1111/bph.15894

DO - 10.1111/bph.15894

M3 - Journal article

C2 - 35710141

VL - 179

SP - 4486

EP - 4499

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 18

ER -

ID: 313055048