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Physiological Regulation of Appetite

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

¹Department of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia, Australia; and ²Department of Gastroenterology, University Hospital, Utrecht, The Netherlands

Submitted 29 October 2004 ; accepted in final form 28 January 2005

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.

cholecystokinin; glucagon-like peptide-1

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