BACKGROUND/AIMS:Glucagon-like peptide-1 (GLP-1) inhibits food intake in animals and humans. Whether GLP-1 interacts with other satiety signals to modulate food intake is unknown. We investigated therefore in healthy volunteers the potential interactions of GLP-1 with signals from the stomach in regulating food intake.METHODS:Three sequential, double-blind, crossover studies were performed in male subjects: (1) 12 subjects underwent four experiments (preloads) 20 min before meal intake; (2) 12 volunteers received intravenous (i.v.) GLP-1 (0.9 pmol/kg/min) or saline; (3) subjects received i.v. GLP-1 or saline (control) together with a preload of either 400 ml water or 400 ml protein shake. The effect of these treatments on food intake and feelings of hunger was quantified. Subjects were free to eat and drink as much as they wished.RESULTS:GLP-1 induced a reduction in food and calorie intake (p < 0.005) compared to controls. If combined with a protein preload, the inhibitory effect of GLP-1 on food intake was markedly increased (p < 0.001). Furthermore, a decrease in hunger feelings and an increase in satiety feelings was documented.CONCLUSION:GLP-1 interacts with signals from the stomach to modulate energy intake in humans. The signal is only initiated by nutrient-based distension, but not with gastric distension of the fundus alone.

Board of Directors Masahiro Asaka, Sapporo Takeshi Azuma, Kobe Tetsuo Arakawa, Osaka Mitsuo Iida, Fukuoka Akinori Iwashita, Fukuoka Kyoji Ogoshi, Kanagawa Michio Kaminishi, Tokyo Sunao Kawano, Osaka Yoshikazu Kinoshita, Shimane Hajime Kuwayama, Saitama Choitsu Sakamoto, Tokyo Kenichi Sugihara, Tokyo Toshiro Sugiyama, Toyama Shin’ichi Takahashi, Tokyo Koji Takeuchi, Kyoto Akira Terano, Tochigi Hirokazu Nagawa, Tokyo Ken Haruma, Kurashiki Kazuma Fujimoto, Saga Takahiro Fujimori, Tochigi Yoshio Hoshihara, Tokyo Michio Hongo, Sendai Hiroyasu Makuuchi, Kanagawa Akihiro Munakata, Aomori Toshikazu Yoshikawa, Kyoto

The limited effectiveness of orlistat, an inhibitor of gastrointestinal lipases, in inhibiting fat digestion is not completely understood. Therefore we studied the effect of orally and duodenally administered orlistat on gastric emptying, cholecystokinin (CCK) secretion, and gallbladder contraction. In healthy males, gastric emptying of solids and fat were quantified scintigraphically, gallbladder contraction by ultrasound and CCK release by radioimmunoassay. Three studies were performed: (1) oral and (2) duodenal orlistat with a fat-containing meal, and (3) duodenal orlistat with a fat-free meal. Gastric emptying rates of solids and fat (T50% accelerated by 16 and by 22%, p< 0.05, respectively) were significantly faster after duodenal perfusion of orlistat; gallbladder contraction and CCK release were reduced under these conditions (p < 0.005, respectively). With oral orlistat no significant effect was documented on these parameters. We conclude that fat hydrolysis is essential in the regulation of fat-induced gastric emptying and gallbladder contraction.