title: Initial evidence that GLP-1 receptor blockade fails to suppress postprandial satiety or promote food intake in humans.
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.
authors: Department of Medicine, Division of General Internal Medicine, University of Washington, 325 Ninth Ave, Box 359780, Seattle, WA 98104, USA.
authors: Susan J
authors: SJ
authors: Melhorn
authors: Department of Medicine, Division of General Internal Medicine, University of Washington, 325 Ninth Ave, Box 359780, Seattle, WA 98104, USA.
authors: Vidhi
authors: V
authors: Tyagi
authors: School of Medicine, Oregon Health & Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
authors: Anne
authors: A
authors: Smeraglio
authors: Division of Endocrinology, Seattle Children's Research Institute, 1900 Ninth Ave, Seattle, WA 98101, USA.
authors: Christian L
authors: CL
authors: Roth
authors: 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.
authors: Ellen A
authors: EA
authors: Schur
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004435:Eating / Q000502:physiology*; D002149:Energy Intake; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000235:genetics; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D006815:Hunger; D054795:Incretins / Q000097:blood; D007328:Insulin / Q000097:blood; D008297:Male; D010446:Peptide Fragments / Q000627:therapeutic use*; D019518:Postprandial Period / Q000502:physiology*; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012527:Satiation / Q000502:physiology*; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D001786:Blood Glucose; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D007328:Insulin; D010446:Peptide Fragments; D018027:Receptors, Glucagon; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1
keywords: GLP-1; Insulin; Satiety; Visual analog scale