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Appetite. 2014 Nov;82:85-90. doi: 10.1016/j.appet.2014.07.009. Epub 2014 Jul 15.

Initial evidence that GLP-1 receptor blockade fails to suppress postprandial satiety or promote food intake in humans.

Author information

1
Department of Medicine, Division of General Internal Medicine, University of Washington, 325 Ninth Ave, Box 359780, Seattle, WA 98104, USA.
2
School of Medicine, Oregon Health & Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
3
Division of Endocrinology, Seattle Children's Research Institute, 1900 Ninth Ave, Seattle, WA 98101, USA.
4
Department of Medicine, Division of General Internal Medicine, University of Washington, 325 Ninth Ave, Box 359780, Seattle, WA 98104, USA. Electronic address: ellschur@u.washington.edu.

Abstract

Glucagon-like peptide 1 (GLP-1) has incretin effects that are well-documented, but the independent role of GLP-1 action in human satiety perception is debated. We hypothesized that blockade of GLP-1 receptors would suppress postprandial satiety and increase voluntary food intake. After an overnight fast, eight normal weight participants (seven men, BMI 19-24.7 kg/m(2), age 19-29 year) were enrolled in a double-blind, placebo-controlled, randomized crossover study of the GLP-1 antagonist Exendin-[9-39] (Ex-9) to determine if the satiating effects of a meal are dependent on GLP-1 signaling in humans. Following a fasting blood draw, iv infusion of Ex-9 (600-750 pmol/kg/min) or saline began. Thirty minutes later, subjects consumed a standardized breakfast followed 90 min later (at the predicted time of maximal endogenous circulating GLP-1) by an ad libitum buffet meal to objectively measure satiety. Infusions ended once the buffet meal was complete. Visual analog scale ratings of hunger and fullness and serial assessments of plasma glucose, insulin, and GLP-1 concentrations were done throughout the experiment. Contrary to the hypothesis, during Ex-9 infusion subjects reported a greater decrease in hunger due to consumption of the breakfast (Ex-9 -62 ± 5; placebo -41 ± 9; P=0.01) than during placebo. There were no differences in ad libitum caloric intake between Ex-9 and placebo. Ex-9 increased glucose, insulin, and endogenous GLP-1, which may have counteracted any effects of Ex-9 infusion to block satiety signaling. Blockade of GLP-1 receptors failed to suppress subjective satiety following a standardized meal or increase voluntary food intake in healthy, normal-weight subjects.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01152333.

KEYWORDS:

GLP-1; Insulin; Satiety; Visual analog scale

PMID:
25049134
PMCID:
PMC4171349
DOI:
10.1016/j.appet.2014.07.009
[Indexed for MEDLINE]
Free PMC Article

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