Small intestinal protein infusion in humans: evidence for a location-specific gradient in intestinal feedback on food intake and GI peptide release

BACKGROUND: Protein infusion in the small intestine results in intestinal brake activation: a negative feedback mechanism that may be mediated by the release of gastrointestinal peptides resulting in a reduction in food intake. It has been proposed that duodenum, jejunum and ileum may respond differently to infused proteins. OBJECTIVE: To investigate differences in ad libitum food intake, feelings of hunger and satiety and the systemic levels of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), glucose and insulin after intraduodenal, intrajejunal and intraileal protein infusion. METHODS: Fourteen subjects (four male, mean age: 23 +/- 2.1 years, mean body mass index: 21.6 +/- 1.8 kg m(-2)) were intubated with a naso-ileal catheter in this double-blind, randomized, placebo-controlled crossover study. Test days (four in total, executed on consecutive days) started with the ingestion of a standardized breakfast, followed by the infusion of 15 g of protein in the duodenum, jejunum or ileum over a period of 60 min. Food intake was measured by offering an ad libitum meal and Visual Analogue Scale (VAS) scores were used to assess feelings of hunger and satiety. Blood samples were drawn at regular intervals for CCK, GLP-1, PYY, glucose and insulin analyses. RESULTS: Intraileal protein infusion decreased ad libitum food intake compared with both intraduodenal and placebo infusion (ileum: 628.5 +/- 63 kcal vs duodenum: 733.6 +/- 50 kcal, P < 0.01 and placebo: 712.2 +/- 53 kcal, P < 0.05). GLP-1 concentrations were increased after ileal infusion compared with jejunal and placebo infusion, whereas CCK concentrations were only increased after intraileal protein infusion compared with placebo. None of the treatments affected VAS scores for hunger and satiety nor plasma concentrations of PYY and glucose. CONCLUSIONS: Protein infusion into the ileum decreases food intake during the next meal compared with intraduodenal infusion, whereas it increases systemic levels of GLP-1 compared with protein infusion into the jejunum and placebo respectively.