Load-dependent effects of duodenal glucose on glycemia, gastrointestinal hormones, antropyloroduodenal motility, and energy intake in healthy men

2007 ◽  
Vol 293 (3) ◽  
pp. E743-E753 ◽  
Author(s):  
Amelia N. Pilichiewicz ◽  
Reawika Chaikomin ◽  
Ixchel M. Brennan ◽  
Judith M. Wishart ◽  
Christopher K. Rayner ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Energy Intake ◽  
Healthy Subjects ◽  
Gastrointestinal Hormones ◽  
Saline Control ◽  
Gastrointestinal Hormone ◽  
Double Blind ◽  
Glucagon Like Peptide 1 ◽  
Glucose Plasma

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 < 0.05 vs. control), with the effect of G4 and G2 being greater than that of G1 ( P < 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 > 0.82, P < 0.05). All glucose infusions suppressed antral ( P < 0.05), but only G4 decreased duodenal, pressure waves ( P < 0.01), resulted in a sustained stimulation of basal pyloric pressure ( P < 0.01), and decreased energy intake ( P < 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.

Subcutaneous glucagon-like peptide-1 (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects

1998 ◽  
Vol 95 (6) ◽  
pp. 719-724 ◽  
Author(s):  
C. Mark B. EDWARDS ◽  
Jeannie F. TODD ◽  
Mohammad A. GHATEI ◽  
Stephen R. BLOOM
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Plasma Glucose ◽  
Healthy Subjects ◽  
Therapeutic Potential ◽  
Double Blind ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

1. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone released postprandially that stimulates insulin secretion, suppresses glucagon secretion and delays gastric emptying. The insulinotropic action of GLP-1 is more potent under hyperglycaemic conditions. Several published studies have indicated the therapeutic potential of subcutaneous GLP-1 in non-insulin-dependent (Type 2) diabetes mellitus. 2. We investigated whether subcutaneous GLP-1, at a dose shown to improve glycaemic control in early Type 2 diabetes, is insulinotropic at normal fasting glucose concentrations. A double-blind, randomized, crossover study of 10 healthy subjects injected with GLP-1 or saline subcutaneously after a 16 h fast was performed. The effect on cardiovascular parameters was also examined. 3. GLP-1 caused a near 5-fold rise in plasma insulin concentration. After treatment with GLP-1, circulating plasma glucose concentrations fell below the normal range in all subjects. One subject had symptoms of hypoglycaemia after GLP-1. A rise in pulse rate was found which correlated with the fall in plasma glucose concentration. An increase in blood pressure occurred with GLP-1 injection which was seen at the same time as the rise in plasma GLP-1 concentrations. 4. This study indicates that subcutaneous GLP-1 can override the normal homoeostatic mechanism maintaining fasting plasma glucose in man, and is also associated with an increase in blood pressure.

scholarly journals Reproducibility of energy intake, gastric emptying, blood glucose, plasma insulin and cholecystokinin responses in healthy young males

2008 ◽  
Vol 101 (7) ◽  
pp. 1094-1102 ◽  
Author(s):  
Nivasinee S. Nair ◽  
Ixchel M. Brennan ◽  
Tanya J. Little ◽  
Diana Gentilcore ◽  
Trygve Hausken ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Gastric Emptying ◽  
Energy Intake ◽  
Plasma Insulin ◽  
Intraclass Correlation ◽  
Young Male ◽  
Gastrointestinal Hormone ◽  
Hormone Release ◽  
Intraindividual Variation ◽  
Glucose Plasma

Gastric emptying, as well as intragastric meal distribution, and gastrointestinal hormones, including cholecystokinin (CCK), play an important role in appetite regulation. The evaluation of gastrointestinal factors regulating food intake is commonly performed in healthy, lean, young male participants. It has, however, been suggested that there is a marked interindividual variability in the effects of nutrient ‘preloads’ on energy intake in this group. Whether there is significant intraindividual variation in acute energy intake after a nutrient preload, and, if so, how this relates to day-to-day differences in gastric emptying and gastrointestinal hormone release, is unclear. The purpose of the present paper is to evaluate the hypothesis that energy intake after a nutrient preload would be reproducible and associated with reproducible patterns of gastric emptying, intragastric distribution and gastrointestinal hormone release. Fifteen healthy men (age 25 (sem5) years) consumed a glucose preload (50 g glucose in 300 ml water; 815 kJ) on three occasions. Gastric emptying and intragastric meal distribution (using three-dimensional ultrasound), blood glucose, plasma insulin and CCK concentrations and appetite perceptions were evaluated over 90 min, and energy intake from a cold buffet-style meal was then quantified. Energy intake was highly reproducible within individuals between visits (intraclass correlation coefficient,ri = 0·9). Gastric emptying, intragastric meal distribution, blood glucose, plasma insulin and CCK concentrations and appetite perceptions did not differ between visits (ri>0·7 for all). In healthy males, energy intake is highly reproducible, at least in the short term, and is associated with reproducible patterns of gastric emptying, glycaemia, insulinaemia and CCK release.

Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans: relationships with body mass index

2014 ◽  
Vol 307 (10) ◽  
pp. G958-G967 ◽  
Author(s):  
Tanya J. Little ◽  
Nicole J. Isaacs ◽  
Richard L. Young ◽  
Raffael Ott ◽  
Nam Q. Nguyen ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Cell Density ◽  
Energy Intake ◽  
Body Mass ◽  
Hormone Secretion ◽  
Gastrointestinal Hormones ◽  
Inverse Correlation ◽  
Duodenal Mucosa ◽  
Gastrointestinal Hormone ◽  
Glucagon Like Peptide 1

Fatty acids (FAs) stimulate the secretion of gastrointestinal hormones, including cholecystokinin (CCK) and glucagon like peptide-1 (GLP-1), which suppress energy intake. In obesity, gastrointestinal responses to FAs are attenuated. Recent studies have identified a key role for the FA-sensing receptors cluster of differentiation (CD)36, G protein-coupled receptor (GPR)40, GPR120, and GPR119 in mediating gastrointestinal hormone secretion. This study aimed to determine the expression and localization of these receptors in the duodenum of humans and to examine relationships with obesity. Duodenal mucosal biopsies were collected from nine lean [body mass index (BMI): 22 ± 1 kg/m2], six overweight (BMI: 28 ± 1 kg/m2), and seven obese (BMI: 49 ± 5 kg/m2) participants. Absolute levels of receptor transcripts were quantified using RT-PCR, while immunohistochemistry was used for localization. Transcripts were expressed in the duodenum of lean, overweight, and obese individuals with abundance of CD36>>GPR40>GPR120>GPR119. Expression levels of GPR120 ( r = 0.46, P = 0.03) and CD36 ( r = 0.69, P = 0.0004) were directly correlated with BMI. There was an inverse correlation between expression of GPR119 with BMI ( r2 = 0.26, P = 0.016). Immunolabeling studies localized CD36 to the brush border membrane of the duodenal mucosa and GPR40, GPR120, and GPR119 to enteroendocrine cells. The number of cells immunolabeled with CCK ( r = −0.54, P = 0.03) and GLP-1 ( r = −0.49, P = 0.045) was inversely correlated with BMI, such that duodenal CCK and GLP-1 cell density decreased with increasing BMI. In conclusion, CD36, GPR40, GPR120, and GPR119 are expressed in the human duodenum. Transcript levels of duodenal FA receptors and enteroendocrine cell density are altered with increasing BMI, suggesting that these changes may underlie decreased gastrointestinal hormone responses to fat and impaired energy intake regulation in obesity.

Effects of varying combinations of intraduodenal lipid and carbohydrate on antropyloroduodenal motility, hormone release, and appetite in healthy males

2009 ◽  
Vol 296 (4) ◽  
pp. R912-R920 ◽  
Author(s):  
Radhika V. Seimon ◽  
Kate L. Feltrin ◽  
James H. Meyer ◽  
Ixchel M. Brennan ◽  
Judith M. Wishart ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Energy Intake ◽  
Peptide Yy ◽  
Gut Hormones ◽  
Double Blind ◽  
Glucose Levels ◽  
Gut Function ◽  
Glucagon Like Peptide 1 ◽  
Desire To Eat ◽  
Healthy Males

Intraduodenal infusions of both lipid and glucose modulate antropyloroduodenal motility and stimulate plasma CCK, with lipid being more potent than glucose. Both stimulate glucagon-like peptide-1, but only lipid stimulates peptide YY (PYY), while only glucose raises blood glucose and stimulates insulin. When administered in combination, lipid and carbohydrate may, thus, have additive effects on energy intake. However, elevated blood glucose levels do not suppress energy intake, and the effect of insulin is controversial. We hypothesized that increasing the ratio of maltodextrin, a complex carbohydrate, relative to lipid would be associated with a reduction in effects on antropyloroduodenal pressures, gut hormones, appetite, and energy intake, when compared with lipid alone. Ten healthy males were studied on three occasions in double-blind, randomized order. Antropyloroduodenal pressures, plasma CCK, PYY and insulin, blood glucose, and appetite were measured during 90-min intraduodenal infusions of 1) 3 kcal/min lipid (L3), 2) 2 kcal/min lipid and 1 kcal/min maltodextrin (L2/CHO1), or 3) 1 kcal/min lipid and 2 kcal/min maltodextrin (L1/CHO2). Energy intake at a buffet lunch consumed immediately after the infusion was quantified. Reducing the lipid (thus, increasing the carbohydrate) content of the infusion was associated with reduced stimulation of basal pyloric pressures ( r = 0.76, P < 0.01), plasma CCK ( r = 0.66, P < 0.01), and PYY ( r = 0.98, P < 0.001), and reduced suppression of antral ( r = −0.64, P < 0.05) and duodenal ( r = −0.69, P < 0.05) pressure waves, desire-to-eat ( r = −0.8, P < 0.001), and energy intake ( r = 0.74, P < 0.01), with no differences in phasic (isolated) pyloric pressures. In conclusion, in healthy males, intraduodenal lipid is a more potent modulator of gut function, associated with greater suppression of energy intake, when compared with isocaloric combinations of lipid and maltodextrin.

Evaluation of interactions between CCK and GLP-1 in their effects on appetite, energy intake, and antropyloroduodenal motility in healthy men

2005 ◽  
Vol 288 (6) ◽  
pp. R1477-R1485 ◽  
Author(s):  
Ixchel M. Brennan ◽  
Kate L. Feltrin ◽  
Michael Horowitz ◽  
Andre J. P. M. Smout ◽  
James H. Meyer ◽  
...  
Keyword(s):  
Energy Intake ◽  
Synergistic Effects ◽  
Isotonic Saline ◽  
Saline Control ◽  
Pressure Waves ◽  
Double Blind ◽  
Healthy Men ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Desire To Eat

There is evidence that CCK and glucagon-like peptide-1 (GLP-1) mediate the effects of nutrients on appetite and gastrointestinal function and that their interaction may be synergistic. We hypothesized that intravenous CCK-8 and GLP-1 would have synergistic effects on appetite, energy intake, and antropyloroduodenal (APD) motility. Nine healthy males (age 22 ± 1 yr) were studied on four separate days in a double-blind, randomized fashion. Appetite and APD pressures were measured during 150-min intravenous infusions of 1) isotonic saline (control), 2) CCK-8 (1.8 pmol·kg−1·min−1), 3) GLP-1 (0.9 pmol·kg−1·min−1), or 4) both CCK-8 (1.8 pmol·kg−1·min−1) and GLP-1 (0.9 pmol·kg−1·min−1). At 120 min, energy intake at a buffet meal was quantified. CCK-8, but not GLP-1, increased fullness, decreased desire to eat and subsequent energy intake, and increased the number and amplitude of isolated pyloric pressure waves and basal pyloric pressure ( P < 0.05). Both CCK-8 and GLP-1 decreased the number of antral and duodenal pressure waves (PWs) ( P < 0.05), and CCK-8+GLP-1 decreased the number of duodenal PWs more than either CCK-8 or GLP-1 alone ( P < 0.02). This was not the case for appetite or isolated pyloric PWs. In conclusion, at the doses evaluated, exogenously administered CCK-8 and GLP-1 had discrepant effects on appetite, energy intake, and APD pressures, and the effects of CCK-8+GLP-1, in combination, did not exceed the sum of the effects of CCK-8 and GLP-1, providing no evidence of synergism.

scholarly journals Acute Effects of Lixisenatide on Energy Intake in Healthy Subjects and Patients with Type 2 Diabetes: Relationship to Gastric Emptying and Intragastric Distribution

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1962 ◽  
Author(s):  
Ryan Jalleh ◽  
Hung Pham ◽  
Chinmay S. Marathe ◽  
Tongzhi Wu ◽  
Madeline D. Buttfield ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Energy Intake ◽  
Double Blind ◽  
Distal Stomach ◽  
Induce Weight Loss ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Intragastric Distribution

Glucagon-like peptide-1 receptor agonists induce weight loss, which has been suggested to relate to the slowing of gastric emptying (GE). In health, energy intake (EI) is more strongly related to the content of the distal, than the total, stomach. We evaluated the effects of lixisenatide on GE, intragastric distribution, and subsequent EI in 15 healthy participants and 15 patients with type 2 diabetes (T2D). Participants ingested a 75-g glucose drink on two separate occasions, 30 min after lixisenatide (10 mcg) or placebo subcutaneously, in a randomised, double-blind, crossover design. GE and intragastric distribution were measured for 180 min followed by a buffet-style meal, where EI was quantified. Relationships of EI with total, proximal, and distal stomach content were assessed. In both groups, lixisenatide slowed GE markedly, with increased retention in both the proximal (p < 0.001) and distal (p < 0.001) stomach and decreased EI (p < 0.001). EI was not related to the content of the total or proximal stomach but inversely related to the distal stomach at 180 min in health on placebo (r = −0.58, p = 0.03) but not in T2D nor after lixisenatide in either group. In healthy and T2D participants, the reduction in EI by lixisenatide is unrelated to changes in GE/intragastric distribution, consistent with a centrally mediated effect.

Effects of the phases of the menstrual cycle on gastric emptying, glycemia, plasma GLP-1 and insulin, and energy intake in healthy lean women

2009 ◽  
Vol 297 (3) ◽  
pp. G602-G610 ◽  
Author(s):  
Ixchel M. Brennan ◽  
Kate L. Feltrin ◽  
Nivasinee S. Nair ◽  
Trygve Hausken ◽  
Tanya J. Little ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Gastric Emptying ◽  
Menstrual Cycle ◽  
Energy Intake ◽  
Luteal Phase ◽  
Follicular Phase ◽  
Phase 2 ◽  
Plasma Hormones ◽  
Glucagon Like Peptide 1 ◽  
Glucose Plasma

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.

Dose-related effects of lauric acid on antropyloroduodenal motility, gastrointestinal hormone release, appetite, and energy intake in healthy men

2005 ◽  
Vol 289 (4) ◽  
pp. R1090-R1098 ◽  
Author(s):  
Tanya J. Little ◽  
Kate L. Feltrin ◽  
Michael Horowitz ◽  
Andre J. P. M. Smout ◽  
Thomas Rades ◽  
...  
Keyword(s):  
Energy Intake ◽  
Lauric Acid ◽  
Hormone Secretion ◽  
Decanoic Acid ◽  
Saline Control ◽  
Gastrointestinal Hormone ◽  
Pressure Waves ◽  
Hormone Release ◽  
Double Blind ◽  
Intraduodenal Infusion

We recently reported that intraduodenal infusion of lauric acid (C12) (0.375 kcal/min, 106 mM) stimulates isolated pyloric pressure waves (IPPWs), inhibits antral and duodenal pressure waves (PWs), stimulates release of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1), and suppresses energy intake and that these effects are much greater than those seen in response to isocaloric decanoic acid (C10) infusion. Administration of C12 was, however, associated with nausea, confounding interpretation of the results. The aim of this study was to evaluate the effects of different intraduodenal doses of C12 on antropyloroduodenal (APD) motility, plasma CCK and GLP-1 concentrations, appetite, and energy intake. Thirteen healthy males were studied on 4 days in double-blind, randomized fashion. APD pressures, plasma CCK and GLP-1 concentrations, and appetite perceptions were measured during 90-min ID infusion of C12 at 0.1 (14 mM), 0.2 (28 mM), or 0.4 (56 mM) kcal/min or saline (control; rate 4 ml/min). Energy intake was determined at a buffet meal immediately following infusion. C12 dose-dependently stimulated IPPWs, decreased antral and duodenal motility, and stimulated secretion of CCK and GLP-1 ( r > 0.4, P < 0.05 for all). C12 (0.4 kcal/min) suppressed energy intake compared with control, C12 (0.1 kcal/min), and C12 (0.2 kcal/min) ( P < 0.05). These effects were observed in the absence of nausea. In conclusion, intraduodenal C12 dose-dependently modulated APD motility and gastrointestinal hormone release in healthy male subjects, whereas effects on energy intake were only apparent with the highest dose infused (0.4 kcal/min), possibly because only at this dose was modulation of APD motility and gastrointestinal hormone secretion sufficient for a suppressant effect on energy intake.

Dose-dependent effects of cholecystokinin-8 on antropyloroduodenal motility, gastrointestinal hormones, appetite, and energy intake in healthy men

2008 ◽  
Vol 295 (6) ◽  
pp. E1487-E1494 ◽  
Author(s):  
Ixchel M. Brennan ◽  
Tanya J. Little ◽  
Kate L. Feltrin ◽  
Andre J. P. M. Smout ◽  
Judith M. Wishart ◽  
...  
Keyword(s):  
Energy Intake ◽  
Gastrointestinal Motility ◽  
Gastrointestinal Hormones ◽  
Saline Control ◽  
Double Blind ◽  
Healthy Men ◽  
Gut Hormone ◽  
Desire To Eat ◽  
Dose Dependent ◽  
Stimulation Of

CCK mediates the effects of nutrients on gastrointestinal motility and appetite. Intravenously administered CCK stimulates pyloric pressures, increases plasma PYY, and suppresses ghrelin, all of which may be important in the regulation of appetite and energy intake. The dose-related effects of exogenous CCK on gastrointestinal motility and gut hormone release, and the relationships between these effects and those on energy intake, are uncertain. We hypothesized that 1) intravenous CCK-8 would have dose-dependent effects on antropyloroduodenal (APD) pressures, plasma PYY and ghrelin concentrations, appetite, and energy intake and 2) the suppression of energy intake by CCK-8 would be related to the stimulation of pyloric motility. Ten healthy men (age 26 ± 2 yr) were studied on four separate occasions in double-blind, randomized fashion. APD pressures, plasma PYY and ghrelin, and appetite were measured during 120-min intravenous infusions of 1) saline (“control”) or 2) CCK-8 at 0.33 (“CCK0.33”), 3) 0.66 (“CCK0.66”), or 4) 2.0 (“CCK2.0”) ng·kg−1·min−1. After 90 min, energy intake at a buffet meal was quantified. CCK-8 dose-dependently stimulated phasic and tonic pyloric pressures and plasma PYY concentrations ( r > 0.70, P < 0.05) and reduced desire to eat and energy intake ( r > −0.60, P < 0.05) without inducing nausea. There were relationships between basal pyloric pressure and isolated pyloric pressure waves (IPPW) with plasma CCK ( r > 0.50, P < 0.01) and between energy intake with IPPW ( r = −0.70, P < 0.05). Therefore, our study demonstrates that exogenous CCK-8 has dose-related effects on APD motility, plasma PYY, desire to eat, and energy intake and suggests that the suppression of energy intake is related to the stimulation of IPPW.

scholarly journals Effects of L-Phenylalanine on Energy Intake and Glycaemia—Impacts on Appetite Perceptions, Gastrointestinal Hormones and Gastric Emptying in Healthy Males

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1788 ◽  
Author(s):  
Penelope C. E. Fitzgerald ◽  
Benoit Manoliu ◽  
Benjamin Herbillon ◽  
Robert E. Steinert ◽  
Michael Horowitz ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Energy Intake ◽  
Plasma Glucose ◽  
Peptide Yy ◽  
Peak Plasma ◽  
Gastrointestinal Hormones ◽  
Postprandial Blood Glucose ◽  
Double Blind ◽  
Glucagon Like Peptide 1 ◽  
Stimulation Of

In humans, phenylalanine stimulates plasma cholecystokinin (CCK) and pyloric pressures, both of which are important in the regulation of energy intake and gastric emptying. Gastric emptying is a key determinant of postprandial blood glucose. We evaluated the effects of intragastric phenylalanine on appetite perceptions and subsequent energy intake, and the glycaemic response to, and gastric emptying of, a mixed-nutrient drink. The study consisted of two parts, each including 16 healthy, lean males (age: 23 ± 1 years). In each part, participants received on three separate occasions, in randomised, double-blind fashion, 5 g (Phe-5 g) or 10g (‘Phe-10 g) L-phenylalanine, or control, intragastrically, 30 min before a standardised buffet-meal (part A), or a standardised mixed-nutrient drink (part B). In part A, plasma CCK and peptide-YY (PYY), and appetite perceptions, were measured at baseline, after phenylalanine alone, and following the buffet-meal, from which energy intake was assessed. In part B, plasma glucose, glucagon-like peptide-1 (GLP-1), insulin and glucagon were measured at baseline, after phenylalanine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured by 13C-acetate breath-test. Phe-10 g, but not Phe-5 g, stimulated plasma CCK (p = 0.01) and suppressed energy intake (p = 0.012); energy intake was correlated with stimulation of CCK (r = −0.4, p = 0.027), and tended to be associated with stimulation of PYY (r = −0.31, p = 0.082). Both Phe-10 g and Phe-5 g stimulated insulin and glucagon (all p < 0.05), but not GLP-1. Phe-10 g, but not Phe-5 g, reduced overall plasma glucose (p = 0.043) and peak plasma glucose (p = 0.017) in response to the mixed-nutrient drink. Phenylalanine had no effect on gastric emptying of the drink. In conclusion, our observations indicate that the energy intake-suppressant effect of phenylalanine is related to the stimulation of CCK and PYY, while the glucoregulatory effect may be independent of stimulation of plasma GLP-1 or slowing of gastric emptying.

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