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...

There is evidence that the menstrual cycle affects appetite, such that energy intake is lower during the follicular compared with the luteal phase. Gastric emptying influences energy intake, glycemia, and plasma glucagon-like peptide-1 (GLP-1), insulin, and cholecystokinin (CCK) release. We hypothesized that 1) gastric emptying of a glucose drink is slower, and glycemia, plasma hormones, hunger, and energy intake are less, during the follicular compared with the luteal phase; 2) the reduction in the latter parameters during the follicular phase are related to slower gastric emptying; and 3) these parameters are reproducible when assessed twice within a particular phase of the menstrual cycle. Nine healthy, lean women were studied on three separate occasions: twice during the follicular phase (days 6-12) and once during the luteal phase (days 18-24). Following consumption of a 300-ml glucose drink (0.17 g/ml), gastric emptying, blood glucose, plasma hormone concentrations, and hunger were measured for 90 min, after which energy intake at a buffet meal was quantified. During the follicular phase, gastric emptying was slower (P < 0.05), and blood glucose (P < 0.01), plasma GLP-1 and insulin (P < 0.05), hunger (P < 0.01), and energy intake (P < 0.05) were lower compared with the luteal phase, with no differences for CCK or between the two follicular phase visits. There were inverse relationships between energy intake, blood glucose, and plasma GLP-1 and insulin concentrations with the amount of glucose drink remaining in the stomach at t = 90 min (r < -0.6, P < 0.05). In conclusion, in healthy women 1) gastric emptying of glucose is slower, and glycemia, plasma GLP-1 and insulin, hunger, and energy intake are less during the follicular compared with the luteal phase; 2) energy intake, glycemia, and plasma GLP-1 and insulin are related to gastric emptying; and 3) these parameters are reproducible when assessed twice during the follicular phase.

Brennan IM, Luscombe-Marsh ND, Seimon RV, Otto B, Horowitz M, Wishart JM, Feinle-Bisset C. Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men. Am J Physiol Gastrointest Liver Physiol 303: G129 -G140, 2012. First published April 30, 2012 doi:10.1152/ajpgi.00478.2011.-While protein is regarded as the most satiating macronutrient, many studies have employed test meals that had very high and unsustainable protein contents. Furthermore, the comparative responses between lean and obese subjects and the relationships between energy intake suppression and gut hormone release remain unclear. We evaluated the acute effects of meals with modest variations in 1) fat, protein, and carbohydrate content and 2) protein load on gastrointestinal hormones, appetite, and subsequent energy intake in lean and obese subjects. Sixteen lean and sixteen obese men were studied on four occasions. Following a standardized breakfast, they received for lunch: 1) high-fat (HF), 2) high-protein (HP), 3) high-carbohydrate/low-protein (HC/LP), or 4) adequateprotein (AP) isocaloric test meals. Hunger, fullness, and gut hormones were measured throughout, and at t ϭ 180 min energy intake at a buffet meal was quantified. In lean subjects, hunger was less and fullness greater following HF, HP, and AP compared with HC/LP meals, and energy intake was less following HF and HP compared with HC meals (P Ͻ 0.05). In the obese subjects, hunger was less following HP compared with HF, HC/LP, and AP meals, and energy intake was less following HP and AP compared with HF and HC meals (P Ͻ 0.05). There were no major differences in hormone responses to the meals among subject groups, but the CCK and ghrelin responses to HP and AP were sustained in both groups. In conclusion, HP meals suppress energy intake in lean and obese subjects, an effect potentially mediated by CCK and ghrelin, while obese individuals appear to be less sensitive to the satiating effects of fat. diet composition; obesity; protein intake; dietary macronutrients; gut hormone release THE CURRENT AVERAGE WESTERN diet derives ϳ50% of energy from carbohydrate, 35% from fat, and 15% from protein (35), which represents a shift toward an increased carbohydrate and reduced protein intake when compared with the diet of our hunter-gatherer ancestors (14). Of the dietary macronutrients, protein is generally regarded as the most satiating nutrient. Accordingly, one dietary strategy for the management of obesity has been to replace some carbohydrate in the diet with protein (2,19,49), although the benefit of this approach remains uncertain (24,29,48). A recent study indicated that in obese subjects weight regain after a 26-wk period was less (by 930 g) in response to a high-protein diet (25% energy from protein), compared with a low-protein diet (13% energy from protein) (29). There is little definitive information about the comparative effects of the three macronutrients or differences in protein l...