Evaluation of interactions between CCK and GLP-1 in their effects on appetite, energy intake, and antropyloroduodenal motility in healthy men

Am J Physiol Regul Integr Comp Physiol. 2005 Jun;288(6):R1477-85. doi: 10.1152/ajpregu.00732.2004. Epub 2005 Feb 3.

Abstract

There is evidence that CCK and glucagon-like peptide-1 (GLP-1) mediate the effects of nutrients on appetite and gastrointestinal function and that their interaction may be synergistic. We hypothesized that intravenous CCK-8 and GLP-1 would have synergistic effects on appetite, energy intake, and antropyloroduodenal (APD) motility. Nine healthy males (age 22 +/- 1 yr) were studied on four separate days in a double-blind, randomized fashion. Appetite and APD pressures were measured during 150-min intravenous infusions of 1) isotonic saline (control), 2) CCK-8 (1.8 pmol.kg(-1).min(-1)), 3) GLP-1 (0.9 pmol.kg(-1).min(-1)), or 4) both CCK-8 (1.8 pmol.kg(-1).min(-1)) and GLP-1 (0.9 pmol.kg(-1).min(-1)). At 120 min, energy intake at a buffet meal was quantified. CCK-8, but not GLP-1, increased fullness, decreased desire to eat and subsequent energy intake, and increased the number and amplitude of isolated pyloric pressure waves and basal pyloric pressure (P < 0.05). Both CCK-8 and GLP-1 decreased the number of antral and duodenal pressure waves (PWs) (P < 0.05), and CCK-8+GLP-1 decreased the number of duodenal PWs more than either CCK-8 or GLP-1 alone (P < 0.02). This was not the case for appetite or isolated pyloric PWs. In conclusion, at the doses evaluated, exogenously administered CCK-8 and GLP-1 had discrepant effects on appetite, energy intake, and APD pressures, and the effects of CCK-8+GLP-1, in combination, did not exceed the sum of the effects of CCK-8 and GLP-1, providing no evidence of synergism.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Appetite / drug effects*
  • Cholecystokinin / blood
  • Cholecystokinin / pharmacology*
  • Double-Blind Method
  • Drug Synergism
  • Duodenum / drug effects
  • Energy Intake / drug effects*
  • Gastrointestinal Motility / drug effects*
  • Glucagon / blood
  • Glucagon / pharmacology*
  • Glucagon-Like Peptide 1
  • Humans
  • Infusions, Intravenous
  • Male
  • Nausea / chemically induced
  • Peptide Fragments / blood
  • Peptide Fragments / pharmacology*
  • Pressure
  • Protein Precursors / blood
  • Protein Precursors / pharmacology*
  • Pyloric Antrum / drug effects
  • Reference Values
  • Satiety Response / drug effects

Substances

  • Peptide Fragments
  • Protein Precursors
  • Glucagon-Like Peptide 1
  • Glucagon
  • Cholecystokinin