GIP and GLP-1 Receptor Antagonism During a Meal in Healthy Individuals

Research output: Contribution to journalJournal articlepeer-review

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GIP and GLP-1 Receptor Antagonism During a Meal in Healthy Individuals. / Gasbjerg, Lærke S.; Helsted, Mads M.; Hartmann, Bolette; Sparre-Ulrich, Alexander H.; Veedfald, Simon; Stensen, Signe; Lanng, Amalie R.; Bergmann, Natasha C.; Christensen, Mikkel B.; Vilsbøll, Tina; Holst, Jens J.; Rosenkilde, Mette M.; Knop, Filip K.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 105, No. 3, 2020, p. e725-e738.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Gasbjerg, LS, Helsted, MM, Hartmann, B, Sparre-Ulrich, AH, Veedfald, S, Stensen, S, Lanng, AR, Bergmann, NC, Christensen, MB, Vilsbøll, T, Holst, JJ, Rosenkilde, MM & Knop, FK 2020, 'GIP and GLP-1 Receptor Antagonism During a Meal in Healthy Individuals', Journal of Clinical Endocrinology and Metabolism, vol. 105, no. 3, pp. e725-e738. https://doi.org/10.1210/clinem/dgz175

APA

Gasbjerg, L. S., Helsted, M. M., Hartmann, B., Sparre-Ulrich, A. H., Veedfald, S., Stensen, S., Lanng, A. R., Bergmann, N. C., Christensen, M. B., Vilsbøll, T., Holst, J. J., Rosenkilde, M. M., & Knop, F. K. (2020). GIP and GLP-1 Receptor Antagonism During a Meal in Healthy Individuals. Journal of Clinical Endocrinology and Metabolism, 105(3), e725-e738. https://doi.org/10.1210/clinem/dgz175

Vancouver

Gasbjerg LS, Helsted MM, Hartmann B, Sparre-Ulrich AH, Veedfald S, Stensen S et al. GIP and GLP-1 Receptor Antagonism During a Meal in Healthy Individuals. Journal of Clinical Endocrinology and Metabolism. 2020;105(3):e725-e738. https://doi.org/10.1210/clinem/dgz175

Author

Gasbjerg, Lærke S. ; Helsted, Mads M. ; Hartmann, Bolette ; Sparre-Ulrich, Alexander H. ; Veedfald, Simon ; Stensen, Signe ; Lanng, Amalie R. ; Bergmann, Natasha C. ; Christensen, Mikkel B. ; Vilsbøll, Tina ; Holst, Jens J. ; Rosenkilde, Mette M. ; Knop, Filip K. / GIP and GLP-1 Receptor Antagonism During a Meal in Healthy Individuals. In: Journal of Clinical Endocrinology and Metabolism. 2020 ; Vol. 105, No. 3. pp. e725-e738.

Bibtex

@article{a917768d692f4828970fbeb8ffb711a5,
title = "GIP and GLP-1 Receptor Antagonism During a Meal in Healthy Individuals",
abstract = "Context: The actions of both endogenous incretin hormones during a meal have not previously been characterized. Objective: Using specific receptor antagonists, we investigated the individual and combined contributions of endogenous glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism, energy expenditure, and gallbladder motility. Design: Randomized, double-blinded, placebo-controlled, crossover design. Setting: On four separate days, four liquid mixed meal tests (1894 kJ) over 270 minutes (min). Patients or Other Participants: Twelve healthy male volunteers. Interventions: Infusions of the GIP receptor antagonist GIP(3-30)NH2 (800 pmol/kg/min), the GLP-1 receptor antagonist exendin(9-39)NH2 (0-20 min: 1000 pmol/kg/min; 20-270 min: 450 pmol/kg/min), GIP(3-30)NH2+exendin(9-39)NH2, or placebo/saline. Main Outcome Measure: Baseline-subtracted area under the curve (bsAUC) of C-peptide. Results: Infusion of GIP(3-30)NH2+exendin(9-39)NH2 significantly increased plasma glucose excursions (bsAUC: 261 ± 142 mmol/L × min) during the liquid mixed meals compared with GIP(3-30)NH2 (180 ± 141 mmol/L × min; P = 0.048), exendin(9-39)NH2 (171 ± 114 mmol/L × min; P = 0.046), and placebo (116 ± 154 mmol/L × min; P = 0.015). Correspondingly, C-peptide:glucose ratios during GIP(3-30)NH2+exendin(9-39)NH2 infusion were significantly lower than during GIP(3-30)NH2 (P = 0.0057), exendin(9-39)NH2 (P = 0.0038), and placebo infusion (P = 0.014). GIP(3-30)NH2 resulted in significantly lower AUCs for glucagon than exendin(9-39)NH2 (P = 0.0417). Gallbladder ejection fraction was higher during GIP(3-30)NH2 compared with placebo (P = 0.004). For all interventions, energy expenditure and respiratory quotient were similar. Conclusions: Endogenous GIP and GLP-1 lower postprandial plasma glucose excursions and stimulate insulin secretion but only endogenous GIP affects gallbladder motility. The two incretin hormones potentiate each other's effects in the control of postprandial glycemia in healthy men.",
keywords = "GIP receptor antagonist, GLP-1 receptor antagonist, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, incretin effect, insulin secretion",
author = "Gasbjerg, {L{\ae}rke S.} and Helsted, {Mads M.} and Bolette Hartmann and Sparre-Ulrich, {Alexander H.} and Simon Veedfald and Signe Stensen and Lanng, {Amalie R.} and Bergmann, {Natasha C.} and Christensen, {Mikkel B.} and Tina Vilsb{\o}ll and Holst, {Jens J.} and Rosenkilde, {Mette M.} and Knop, {Filip K.}",
year = "2020",
doi = "10.1210/clinem/dgz175",
language = "English",
volume = "105",
pages = "e725--e738",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "3",

}

RIS

TY - JOUR

T1 - GIP and GLP-1 Receptor Antagonism During a Meal in Healthy Individuals

AU - Gasbjerg, Lærke S.

AU - Helsted, Mads M.

AU - Hartmann, Bolette

AU - Sparre-Ulrich, Alexander H.

AU - Veedfald, Simon

AU - Stensen, Signe

AU - Lanng, Amalie R.

AU - Bergmann, Natasha C.

AU - Christensen, Mikkel B.

AU - Vilsbøll, Tina

AU - Holst, Jens J.

AU - Rosenkilde, Mette M.

AU - Knop, Filip K.

PY - 2020

Y1 - 2020

N2 - Context: The actions of both endogenous incretin hormones during a meal have not previously been characterized. Objective: Using specific receptor antagonists, we investigated the individual and combined contributions of endogenous glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism, energy expenditure, and gallbladder motility. Design: Randomized, double-blinded, placebo-controlled, crossover design. Setting: On four separate days, four liquid mixed meal tests (1894 kJ) over 270 minutes (min). Patients or Other Participants: Twelve healthy male volunteers. Interventions: Infusions of the GIP receptor antagonist GIP(3-30)NH2 (800 pmol/kg/min), the GLP-1 receptor antagonist exendin(9-39)NH2 (0-20 min: 1000 pmol/kg/min; 20-270 min: 450 pmol/kg/min), GIP(3-30)NH2+exendin(9-39)NH2, or placebo/saline. Main Outcome Measure: Baseline-subtracted area under the curve (bsAUC) of C-peptide. Results: Infusion of GIP(3-30)NH2+exendin(9-39)NH2 significantly increased plasma glucose excursions (bsAUC: 261 ± 142 mmol/L × min) during the liquid mixed meals compared with GIP(3-30)NH2 (180 ± 141 mmol/L × min; P = 0.048), exendin(9-39)NH2 (171 ± 114 mmol/L × min; P = 0.046), and placebo (116 ± 154 mmol/L × min; P = 0.015). Correspondingly, C-peptide:glucose ratios during GIP(3-30)NH2+exendin(9-39)NH2 infusion were significantly lower than during GIP(3-30)NH2 (P = 0.0057), exendin(9-39)NH2 (P = 0.0038), and placebo infusion (P = 0.014). GIP(3-30)NH2 resulted in significantly lower AUCs for glucagon than exendin(9-39)NH2 (P = 0.0417). Gallbladder ejection fraction was higher during GIP(3-30)NH2 compared with placebo (P = 0.004). For all interventions, energy expenditure and respiratory quotient were similar. Conclusions: Endogenous GIP and GLP-1 lower postprandial plasma glucose excursions and stimulate insulin secretion but only endogenous GIP affects gallbladder motility. The two incretin hormones potentiate each other's effects in the control of postprandial glycemia in healthy men.

AB - Context: The actions of both endogenous incretin hormones during a meal have not previously been characterized. Objective: Using specific receptor antagonists, we investigated the individual and combined contributions of endogenous glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism, energy expenditure, and gallbladder motility. Design: Randomized, double-blinded, placebo-controlled, crossover design. Setting: On four separate days, four liquid mixed meal tests (1894 kJ) over 270 minutes (min). Patients or Other Participants: Twelve healthy male volunteers. Interventions: Infusions of the GIP receptor antagonist GIP(3-30)NH2 (800 pmol/kg/min), the GLP-1 receptor antagonist exendin(9-39)NH2 (0-20 min: 1000 pmol/kg/min; 20-270 min: 450 pmol/kg/min), GIP(3-30)NH2+exendin(9-39)NH2, or placebo/saline. Main Outcome Measure: Baseline-subtracted area under the curve (bsAUC) of C-peptide. Results: Infusion of GIP(3-30)NH2+exendin(9-39)NH2 significantly increased plasma glucose excursions (bsAUC: 261 ± 142 mmol/L × min) during the liquid mixed meals compared with GIP(3-30)NH2 (180 ± 141 mmol/L × min; P = 0.048), exendin(9-39)NH2 (171 ± 114 mmol/L × min; P = 0.046), and placebo (116 ± 154 mmol/L × min; P = 0.015). Correspondingly, C-peptide:glucose ratios during GIP(3-30)NH2+exendin(9-39)NH2 infusion were significantly lower than during GIP(3-30)NH2 (P = 0.0057), exendin(9-39)NH2 (P = 0.0038), and placebo infusion (P = 0.014). GIP(3-30)NH2 resulted in significantly lower AUCs for glucagon than exendin(9-39)NH2 (P = 0.0417). Gallbladder ejection fraction was higher during GIP(3-30)NH2 compared with placebo (P = 0.004). For all interventions, energy expenditure and respiratory quotient were similar. Conclusions: Endogenous GIP and GLP-1 lower postprandial plasma glucose excursions and stimulate insulin secretion but only endogenous GIP affects gallbladder motility. The two incretin hormones potentiate each other's effects in the control of postprandial glycemia in healthy men.

KW - GIP receptor antagonist

KW - GLP-1 receptor antagonist

KW - glucagon-like peptide-1

KW - glucose-dependent insulinotropic polypeptide

KW - incretin effect

KW - insulin secretion

U2 - 10.1210/clinem/dgz175

DO - 10.1210/clinem/dgz175

M3 - Journal article

C2 - 32077470

AN - SCOPUS:85079754374

VL - 105

SP - e725-e738

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 3

ER -

ID: 243524331