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

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

Standard

Dose-dependent efficacy of the glucose-dependent insulinotropic polypeptide (GIP)receptor antagonistGIP(3-30)NH2 on GIP actions in humans. / Gasbjerg, Laerke Smidt; Bari, Emilie J.; Stensen, Signe; Hoe, Bjorn; Lanng, Amalie R.; Mathiesen, David S.; Christensen, Mikkel B.; Hartmann, Bolette; Holst, Jens J.; Rosenkilde, Mette M.; Knop, Filip Krag.

In: Diabetes, Obesity and Metabolism, Vol. 23, No. 1, 2021, p. 68-74.

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

Harvard

Gasbjerg, LS, Bari, EJ, Stensen, S, Hoe, B, Lanng, AR, Mathiesen, DS, Christensen, MB, Hartmann, B, Holst, JJ, Rosenkilde, MM & Knop, FK 2021, 'Dose-dependent efficacy of the glucose-dependent insulinotropic polypeptide (GIP)receptor antagonistGIP(3-30)NH2 on GIP actions in humans', Diabetes, Obesity and Metabolism, vol. 23, no. 1, pp. 68-74. https://doi.org/10.1111/dom.14186

APA

Gasbjerg, L. S., Bari, E. J., Stensen, S., Hoe, B., Lanng, A. R., Mathiesen, D. S., Christensen, M. B., Hartmann, B., Holst, J. J., Rosenkilde, M. M., & Knop, F. K. (2021). Dose-dependent efficacy of the glucose-dependent insulinotropic polypeptide (GIP)receptor antagonistGIP(3-30)NH2 on GIP actions in humans. Diabetes, Obesity and Metabolism, 23(1), 68-74. https://doi.org/10.1111/dom.14186

Vancouver

Gasbjerg LS, Bari EJ, Stensen S, Hoe B, Lanng AR, Mathiesen DS et al. Dose-dependent efficacy of the glucose-dependent insulinotropic polypeptide (GIP)receptor antagonistGIP(3-30)NH2 on GIP actions in humans. Diabetes, Obesity and Metabolism. 2021;23(1):68-74. https://doi.org/10.1111/dom.14186

Author

Gasbjerg, Laerke Smidt ; Bari, Emilie J. ; Stensen, Signe ; Hoe, Bjorn ; Lanng, Amalie R. ; Mathiesen, David S. ; Christensen, Mikkel B. ; Hartmann, Bolette ; Holst, Jens J. ; Rosenkilde, Mette M. ; Knop, Filip Krag. / Dose-dependent efficacy of the glucose-dependent insulinotropic polypeptide (GIP)receptor antagonistGIP(3-30)NH2 on GIP actions in humans. In: Diabetes, Obesity and Metabolism. 2021 ; Vol. 23, No. 1. pp. 68-74.

Bibtex

@article{01c18cb0557e4f6784b526d664d6d9d0,
title = "Dose-dependent efficacy of the glucose-dependent insulinotropic polypeptide (GIP)receptor antagonistGIP(3-30)NH2 on GIP actions in humans",
abstract = "The glucose-dependent insulinotropic polypeptide (GIP) fragment GIP(3-30)NH(2)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)NH(2)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)NH(2)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)NH(2)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 = "dose-response relationship, GIP, GIP receptor antagonist, incretin therapy, pharmacodynamics, GASTRIC-INHIBITORY POLYPEPTIDE, GIP RECEPTOR, GIP(3-30)NH2, ANTAGONIST",
author = "Gasbjerg, {Laerke Smidt} and Bari, {Emilie J.} and Signe Stensen and Bjorn Hoe and Lanng, {Amalie R.} and Mathiesen, {David S.} and Christensen, {Mikkel B.} and Bolette Hartmann and Holst, {Jens J.} and Rosenkilde, {Mette M.} and Knop, {Filip Krag}",
year = "2021",
doi = "10.1111/dom.14186",
language = "English",
volume = "23",
pages = "68--74",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
publisher = "Wiley-Blackwell",
number = "1",

}

RIS

TY - JOUR

T1 - Dose-dependent efficacy of the glucose-dependent insulinotropic polypeptide (GIP)receptor antagonistGIP(3-30)NH2 on GIP actions in humans

AU - Gasbjerg, Laerke Smidt

AU - Bari, Emilie J.

AU - Stensen, Signe

AU - Hoe, Bjorn

AU - Lanng, Amalie R.

AU - Mathiesen, David S.

AU - Christensen, Mikkel B.

AU - Hartmann, Bolette

AU - Holst, Jens J.

AU - Rosenkilde, Mette M.

AU - Knop, Filip Krag

PY - 2021

Y1 - 2021

N2 - The glucose-dependent insulinotropic polypeptide (GIP) fragment GIP(3-30)NH(2)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)NH(2)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)NH(2)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)NH(2)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.

AB - The glucose-dependent insulinotropic polypeptide (GIP) fragment GIP(3-30)NH(2)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)NH(2)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)NH(2)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)NH(2)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.

KW - dose-response relationship

KW - GIP

KW - GIP receptor antagonist

KW - incretin therapy

KW - pharmacodynamics

KW - GASTRIC-INHIBITORY POLYPEPTIDE

KW - GIP RECEPTOR

KW - GIP(3-30)NH2

KW - ANTAGONIST

U2 - 10.1111/dom.14186

DO - 10.1111/dom.14186

M3 - Journal article

C2 - 32886401

VL - 23

SP - 68

EP - 74

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 1

ER -

ID: 249862811