Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2021 Jan;23(1):68-74.
doi: 10.1111/dom.14186. Epub 2020 Oct 1.

Dose-dependent efficacy of the glucose-dependent insulinotropic polypeptide (GIP) receptor antagonist GIP(3-30)NH2 on GIP actions in humans

Laerke Smidt Gasbjerg  1   2 , Emilie J Bari  2 , Signe Stensen  2   3 , Bjørn Hoe  2   3 , Amalie R Lanng  2   3 , David S Mathiesen  2 , Mikkel B Christensen  2   3   4 , Bolette Hartmann  1   5 , Jens J Holst  1   5 , Mette M Rosenkilde  1   5 , Filip Krag Knop  2   3   5   6
Affiliations
Randomized Controlled Trial

Dose-dependent efficacy of the glucose-dependent insulinotropic polypeptide (GIP) receptor antagonist GIP(3-30)NH2 on GIP actions in humans

Laerke Smidt Gasbjerg et al. Diabetes Obes Metab. 2021 Jan.

Abstract

The glucose-dependent insulinotropic polypeptide (GIP) fragment GIP(3-30)NH2 is a selective, competitive GIP receptor antagonist, and doses of 800 to 1200 pmol/kg/min inhibit GIP-induced potentiation of glucose-stimulated insulin secretion by >80% in humans. We evaluated the effects of GIP(3-30)NH2 across a wider dose range in eight healthy men undergoing six separate and randomized 10-mmol/L hyperglycaemic clamps (A-F) with concomitant intravenous infusion of GIP (1.5 pmol/kg/min; A-E) or saline (F). Clamps A to E involved double-blinded, infusions of saline (A) and GIP(3-30)NH2 at four rates: 2 (B), 20 (C), 200 (D) and 2000 pmol/kg/min (E), respectively. Mean plasma concentrations of glucose (A-F) and GIP (A-E) were similar. GIP-induced potentiation of glucose-stimulated insulin secretion was reduced by 44 ± 10% and 84 ± 10% during clamps D and E, respectively. Correspondingly, the amounts of glucose required to maintain the clamp during D and E were not different from F. GIP-induced suppression of bone resorption and increase in heart rate were lowered by clamps D and E. In conclusion, GIP(3-30)NH2 provides extensive, dose-dependent inhibition of the GIP receptor in humans, with most pronounced effects of the doses 200 to 2000 pmol/kg/min within the tested range.

Keywords: GIP; GIP receptor antagonist; dose-response relationship; incretin therapy; pharmacodynamics.

PubMed Disclaimer

References

REFERENCES

    1. Dupre J, Ross SA, Watson D, Brown JC. Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrinol Metab. 1973;37:826-828.
    1. Gasbjerg LS, Bergmann NC, Stensen S, et al. Evaluation of the incretin effect in humans using GIP and GLP-1 receptor antagonists. Peptides. 2019;125:1-10.
    1. Nauck MA, Meier JJ. Incretin hormones: their role in health and disease. Diabetes Obes Metab. 2018;20(October 2017):5-21.
    1. Gasbjerg LS, Helsted MM, Hartmann B, et al. Separate and combined gluco-metabolic effects of endogenous glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 in healthy individuals. Diabetes. 2019;68:906-917.
    1. Gasbjerg LS, Helsted MM, Hartmann B, et al. GIP and GLP-1 receptor antagonism during a meal in healthy individuals. J Clin Endocrinol Metab. 2020;105(3):1-14.

Publication types

LinkOut - more resources