GIP and GLP-1 Receptor Antagonism During a Meal in Healthy Individuals
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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.
I: Journal of Clinical Endocrinology and Metabolism, Bind 105, Nr. 3, 2020, s. e725-e738.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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