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Updated: Sep 7, 2025

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
Glucose-dependent insulinotropic polypeptide receptor antagonist treatment causes a reduction in weight gain in
Geke Aline Boer1,2, Jenna Elizabeth Hunt1,2, Maria Buur Nordskov Gabe2
1Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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.
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