title: Effect of Oxyntomodulin, Glucagon, GLP-1, and Combined Glucagon +GLP-1 Infusion on Food Intake, Appetite, and Resting Energy Expenditure.
abstract: BACKGROUND
  The gut hormone, oxyntomodulin, is a proglucagon product with body weight-lowering potential. It binds to both the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor; however, the mechanism behind the body weight-lowering effect remains elusive.
  
  
  OBJECTIVE
  We wanted to delineate the contributions of separate and combined GLP-1 receptor and glucagon receptor activation to the body weight-reducing mechanisms of oxyntomodulin.
  
  
  METHODS
  This was a double-blinded, randomized, crossover study.
  
  
  METHODS
  The study was conducted at a specialized research unit.
  
  
  METHODS
  Fifteen young healthy male volunteers (aged 22 [range 18-32] y; body mass index 23 [21-26] kg/m(2); fasting plasma glucose 5.1 [4.4-5.4] mmol/L; and glycated hemoglobin A1c 40 (37-42) mmol/mol).
  
  
  METHODS
  Five 4-hour liquid meal tests during the infusion of saline, GLP-1 (1 pmol × kg(-1) × min(-1)), glucagon (0.86 pmol × kg(-1) × min(-1)), oxyntomodulin (3 pmol × kg(-1) × min(-1)), or glucagon+GLP-1 (same doses).
  
  
  METHODS
  We evaluated resting energy expenditure (measured as oxygen uptake, gastric emptying (GE), composite appetite scores (CAS), and food intake.
  
  
  RESULTS
  Oxyntomodulin, GLP-1, and GLP-1+glucagon slowed GE and reduced CAS, whereas glucagon did not affect GE and CAS. All infusions caused a similar decrease in food intake compared with saline (total intake (g [95% confidence interval]), saline 811 [729, 892], GLP-1 669 [586, 750], glucagon 686 [604, 768], oxyntomodulin 689 [608, 771], and glucagon+GLP-1 688 [606, 769]). Oxygen uptake did not change significantly from baseline in response to any peptide infusion compared with saline.
  
  
  CONCLUSIONS
  Oxyntomodulin, GLP-1, and glucagon decreased food intake but with no additional effect of combining GLP-1 and glucagon.
authors.affiliation: Center for Diabetes Research (J.I.B., F.K.K., T.V.), Gentofte Hospital, and NNF Center for Basic Metabolic Research and Department of Biomedical Sciences (J.I.B., J.J.H., B.H., F.K.K.), Faculty of Health Sciences, University of Copenhagen, DK-2900 Hellerup, Denmark; and Diabetes Research Unit (B.A.), Novo Nordisk A/S, DK-2760 Måløv, Denmark.
authors.forename: Jonatan Ising
authors.initials: JI
authors.lastname: Bagger
authors.affiliation: Center for Diabetes Research (J.I.B., F.K.K., T.V.), Gentofte Hospital, and NNF Center for Basic Metabolic Research and Department of Biomedical Sciences (J.I.B., J.J.H., B.H., F.K.K.), Faculty of Health Sciences, University of Copenhagen, DK-2900 Hellerup, Denmark; and Diabetes Research Unit (B.A.), Novo Nordisk A/S, DK-2760 Måløv, Denmark.
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Center for Diabetes Research (J.I.B., F.K.K., T.V.), Gentofte Hospital, and NNF Center for Basic Metabolic Research and Department of Biomedical Sciences (J.I.B., J.J.H., B.H., F.K.K.), Faculty of Health Sciences, University of Copenhagen, DK-2900 Hellerup, Denmark; and Diabetes Research Unit (B.A.), Novo Nordisk A/S, DK-2760 Måløv, Denmark.
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Center for Diabetes Research (J.I.B., F.K.K., T.V.), Gentofte Hospital, and NNF Center for Basic Metabolic Research and Department of Biomedical Sciences (J.I.B., J.J.H., B.H., F.K.K.), Faculty of Health Sciences, University of Copenhagen, DK-2900 Hellerup, Denmark; and Diabetes Research Unit (B.A.), Novo Nordisk A/S, DK-2760 Måløv, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Andersen
authors.affiliation: Center for Diabetes Research (J.I.B., F.K.K., T.V.), Gentofte Hospital, and NNF Center for Basic Metabolic Research and Department of Biomedical Sciences (J.I.B., J.J.H., B.H., F.K.K.), Faculty of Health Sciences, University of Copenhagen, DK-2900 Hellerup, Denmark; and Diabetes Research Unit (B.A.), Novo Nordisk A/S, DK-2760 Måløv, Denmark.
authors.forename: Filip Krag
authors.initials: FK
authors.lastname: Knop
authors.affiliation: Center for Diabetes Research (J.I.B., F.K.K., T.V.), Gentofte Hospital, and NNF Center for Basic Metabolic Research and Department of Biomedical Sciences (J.I.B., J.J.H., B.H., F.K.K.), Faculty of Health Sciences, University of Copenhagen, DK-2900 Hellerup, Denmark; and Diabetes Research Unit (B.A.), Novo Nordisk A/S, DK-2760 Måløv, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
mesh_terms: D000082:Acetaminophen / Q000097:blood / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000097:blood / Q000494:pharmacology; D001066:Appetite / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D005746:Gastric Emptying / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D053772:Oxyntomodulin / Q000494:pharmacology*; D012146:Rest / Q000502:physiology; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D053772:Oxyntomodulin; D000082:Acetaminophen; D052216:Glucagon-Like Peptide 1; D005934:Glucagon