The rate of gastric emptying of glucose-containing liquids is a major determinant of postprandial glycemia. The latter is also dependent on stimulation of insulin secretion by glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). While overall emptying of glucose approximates 1-3 kcal/min, the "early phase" of gastric emptying is usually more rapid. We have evaluated the hypothesis that increased stimulation of incretin hormones and insulin by a more rapid initial rate of small intestinal glucose delivery would reduce the overall glycemic response to a standardized enteral glucose load. 12 healthy subjects were studied on two separate days on which they received an intraduodenal (ID) glucose infusion for 120 min; on one day the infusion rate was variable, being more rapid (6 kcal/min) between t = 0-10 min and slower (0.55 kcal/min) between t = 10-120 min, whereas, on the other day, the rate was constant (1 kcal/min) from t = 0-120 min, ie on both days 120 kcal were given. Between t = 0-75 min plasma insulin, GIP and GLP-1 were higher with the variable infusion. Despite the increase in insulin and incretin hormones, blood glucose levels were also higher. Between t = 75-180 min blood glucose and plasma insulin were lower with the variable infusion. There was no difference in the area under the curve (AUC) 0-180 min for blood glucose. We conclude that stimulation of incretin hormone and insulin release by a more rapid initial rate of ID glucose delivery does not lead to an overall reduction in glycemia in healthy subjects.