Evaluation of interactions between CCK and GLP-1 in their effects on appetite, energy intake, and antropyloroduodenal motility in healthy men.
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.
Brennan
Ixchel M
IM
Department of Medicine, University of Adelaide, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia.
Feltrin
Kate L
KL
Horowitz
Michael
M
Smout
Andre J P M
AJ
Meyer
James H
JH
Wishart
Judith
J
Feinle-Bisset
Christine
C
D000293:Adolescent; D000328:Adult; D001066:Appetite / Q000187:drug effects*; D002766:Cholecystokinin / Q000097:blood / Q000494:pharmacology*; D004311:Double-Blind Method; D004357:Drug Synergism; D004386:Duodenum / Q000187:drug effects; D002149:Energy Intake / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005934:Glucagon / Q000097:blood / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009325:Nausea / Q000139:chemically induced; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology*; D011312:Pressure; D011498:Protein Precursors / Q000097:blood / Q000494:pharmacology*; D011706:Pyloric Antrum / Q000187:drug effects; D012016:Reference Values; D012528:Satiety Response / Q000187:drug effects
D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002766:Cholecystokinin