Load-dependent effects of duodenal glucose on glycemia, gastrointestinal hormones, antropyloroduodenal motility, and energy intake in healthy men. Am J Physiol Endocrinol Metab 293: E743-E753, 2007. First published July 3, 2007; doi:10.1152/ajpendo.00159.2007.-Gastric emptying is a major determinant of glycemia, gastrointestinal hormone release, and appetite. We determined the effects of different intraduodenal glucose loads on glycemia, insulinemia, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and cholecystokinin (CCK), antropyloroduodenal motility, and energy intake in healthy subjects. Blood glucose, plasma hormone, and antropyloroduodenal motor responses to 120-min intraduodenal infusions of glucose at 1) 1 ("G1"), 2) 2 ("G2"), and 3) 4 ("G4") kcal/min or of 4) saline ("control") were measured in 10 healthy males in double-blind, randomized fashion. Immediately after each infusion, energy intake at a buffet meal was quantified. Blood glucose rose in response to all glucose infusions (P Ͻ 0.05 vs. control), with the effect of G4 and G2 being greater than that of G1 (P Ͻ 0.05) but with no difference between G2 and G4. The rises in insulin, GLP-1, GIP, and CCK were related to the glucose load (r Ͼ 0.82, P Ͻ 0.05). All glucose infusions suppressed antral (P Ͻ 0.05), but only G4 decreased duodenal, pressure waves (P Ͻ 0.01), resulted in a sustained stimulation of basal pyloric pressure (P Ͻ 0.01), and decreased energy intake (P Ͻ 0.05). In conclusion, variations in duodenal glucose loads have differential effects on blood glucose, plasma insulin, GLP-1, GIP and CCK, antropyloroduodenal motility, and energy intake in healthy subjects. These observations have implications for strategies to minimize postprandial glycemic excursions in type 2 diabetes. insulinemia; incretin hormones THE RATE OF GASTRIC EMPTYING of carbohydrate, particularly glucose, has an impact on glycemia (25), appetite (9, 31), and energy intake (32). In healthy subjects, glucose solutions are known to empty from the stomach in an overall linear rate of ϳ2-3 kcal/min (24); this tight regulation results primarily from a length-dependent feedback arising from the small intestine (34), which in turn modulates antropyloroduodenal motility and is associated with the release of a number of gastrointestinal hormones, including cholecystokinin (CCK) (33) and the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) (32,41,51). The relationships of glycemia, hormone release, and changes in gastric motility with the duodenal glucose load, particularly the time course of these effects, are poorly defined.The rate of gastric emptying is a major determinant of the glycemic response to a meal; even relatively minor changes in small intestinal glucose delivery may have major effects on glycemic and insulinemic responses in healthy subjects (7) and non-insulin-treated type 2 diabetics (41). In type 1 diabetes, the initial postprandial insulin requirement is less when gastri...