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.

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.

Load-dependent effects of duodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, and energy intake in healthy men

2007 ◽  
Vol 293 (6) ◽  
pp. R2170-R2178 ◽  
Author(s):  
Amelia N. Pilichiewicz ◽  
Penny Papadopoulos ◽  
Ixchel M. Brennan ◽  
Tanya J. Little ◽  
James H. Meyer ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Energy Intake ◽  
Peptide Yy ◽  
Saline Control ◽  
Double Blind ◽  
Gastric Emptying Rate ◽  
The Mean ◽  
Small Intestinal ◽  
Healthy Males ◽  
Cck Release

Both load and duration of small intestinal lipid infusion affect antropyloroduodenal motility and CCK and peptide YY (PYY) release at loads comparable to and higher than the normal gastric emptying rate. We determined 1) the effects of intraduodenal lipid loads well below the mean rate of gastric emptying on, and 2) the relationships between antropyloroduodenal motility, CCK, PYY, appetite, and energy intake. Sixteen healthy males were studied on four occasions in double-blind, randomized fashion. Antropyloroduodenal motility, plasma CCK and PYY, and appetite perceptions were measured during 50-min IL (Intralipid) infusions at: 0.25 (IL0.25), 1.5 (IL1.5), and 4 (IL4) kcal/min or saline (control), after which energy intake at a buffet meal was quantified. IL0.25 stimulated isolated pyloric pressure waves (PWs) and CCK release, albeit transiently, and suppressed antral PWs, PW sequences, and hunger ( P < 0.05) but had no effect on basal pyloric pressure or PYY when compared with control. Loads ≥ 1.5 kcal/min were required for the stimulation of basal pyloric pressures and PYY and suppression of duodenal PWs ( P < 0.05). All of these effects were related to the lipid load ( R > 0.5 or < −0.5, P < 0.05). Only IL4 reduced energy intake (in kcal: control, 1,289 ± 62; IL0.25, 1,282 ± 44; IL1.5, 1,235 ± 71; and IL4, 1,139 ± 65 compared with control and IL0.25, P < 0.05). In conclusion, in healthy males the effects of intraduodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, appetite, and energy intake are load dependent, and the threshold loads required to elicit responses vary for these parameters.

scholarly journals Acute Effects of Substitution, and Addition, of Carbohydrates and Fat to Protein on Gastric Emptying, Blood Glucose, Gut Hormones, Appetite, and Energy Intake

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1451 ◽  
Author(s):  
Caroline Giezenaar ◽  
Kylie Lange ◽  
Trygve Hausken ◽  
Karen Jones ◽  
Michael Horowitz ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Gastric Emptying ◽  
Olive Oil ◽  
Whey Protein ◽  
Energy Intake ◽  
Young Men ◽  
Gut Hormones ◽  
Double Blind ◽  
Gut Hormone ◽  
G 28

Whey protein, when ingested on its own, load-dependently slows gastric emptying and stimulates gut hormone concentrations in healthy young men. The aim of this study was to determine the effects of substitution, and addition, of carbohydrate (dextrose) and fat (olive oil) to whey protein. In randomized, double-blind order, 13 healthy young men (age: 23 ± 1 years, body mass index: 24 ± 1 kg/m2) ingested a control drink (450 mL; ~2 kcal/‘control’) or iso-volumetric drinks containing protein/carbohydrate/fat: (i) 14 g/28 g/12.4 g (280 kcal/‘M280′), (ii) 70 g/28 g/12.4 g (504kcal/‘M504′), and (iii) 70 g/0 g/0 g (280 kcal/‘P280′), on 4 separate study days. Gastric emptying (n = 11, 3D-ultrasonography), blood glucose, plasma insulin, ghrelin, cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) concentrations (0–180 min), appetite (visual analogue scales), and ad-libitum buffet-meal energy intake (180–210 min) were determined. Substitution of protein with carbohydrate and fat was associated with faster gastric emptying (lower 50% emptying time (T50)), reduced suppression of ghrelin, and stimulation of GLP-1 (all P < 0.001); while the addition of carbohydrate and fat to protein did not affect gastric emptying or gut hormone responses significantly. Total energy intake (i.e., drink plus meal) was greater after all caloric drinks than control (P < 0.001). In conclusion, substitution of whey protein with dextrose and olive oil accelerated gastric emptying. Higher protein content of a mixed macronutrient drink increased gut hormone and insulin responses.

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 The Effect of a Subcutaneous Infusion of GLP-1, OXM, and PYY on Energy Intake and Expenditure in Obese Volunteers

2017 ◽  
Vol 102 (7) ◽  
pp. 2364-2372 ◽  
Author(s):  
Tricia Tan ◽  
Preeshila Behary ◽  
George Tharakan ◽  
James Minnion ◽  
Werd Al-Najim ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Energy Intake ◽  
Peptide Yy ◽  
Gut Hormones ◽  
Resting Energy Expenditure ◽  
Subcutaneous Infusion ◽  
Glucagon Like Peptide 1 ◽  
Treatment Of Obesity ◽  
First Time

Abstract Background: Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment of obesity, although limited by availability and operative risk. The gut hormones Glucagon-like peptide-1 (GLP-1), Peptide YY (PYY), and Oxyntomodulin (OXM) are elevated postprandially after RYGB, which has been postulated to contribute to its metabolic benefits. Objective: We hypothesized that infusion of the three gut hormones to achieve levels similar to those encountered postprandially in RYGB patients might be effective in suppressing appetite. The aim of this study was to investigate the effect of a continuous infusion of GLP-1, OXM, and PYY (GOP) on energy intake and expenditure in obese volunteers. Methods: Obese volunteers were randomized to receive an infusion of GOP or placebo in a single-blinded, randomized, placebo-controlled crossover study for 10.5 hours a day. This was delivered subcutaneously using a pump device, allowing volunteers to remain ambulatory. Ad libitum food intake studies were performed during the infusion, and energy expenditure was measured using a ventilated hood calorimeter. Results: Postprandial levels of GLP-1, OXM, and PYY seen post RYGB were successfully matched using 4 pmol/kg/min, 4 pmol/kg/min, and 0.4 pmol/kg/min, respectively. This dose led to a mean reduction of 32% in food intake. No significant effects on resting energy expenditure were observed. Conclusion: This is, to our knowledge, the first time that an acute continuous subcutaneous infusion of GOP, replicating the postprandial levels observed after RYGB, is shown to be safe and effective in reducing food intake. This data suggests that triple hormone therapy might be a useful tool against obesity.

scholarly journals Incretin secretion in humans is under the influence of cannabinoid receptors

2017 ◽  
Vol 313 (3) ◽  
pp. E359-E366 ◽  
Author(s):  
Chee W. Chia ◽  
Olga D. Carlson ◽  
David D. Liu ◽  
Isabel González-Mariscal ◽  
Sara Santa-Cruz Calvo ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Gut Hormones ◽  
Tolerance Test ◽  
Crossover Fashion ◽  
Oral Glucose ◽  
Post Dose ◽  
Double Blind ◽  
Glucose Levels ◽  
Incretin Secretion ◽  
Glucagon Like Peptide 1

The mechanisms regulating incretin secretion are not fully known. Human obesity is associated with altered incretin secretion and elevated endocannabinoid levels. Since cannabinoid receptors (CBRs) are expressed on incretin-secreting cells in rodents, we hypothesized that endocannabinoids are involved in the regulation of incretin secretion. We compared plasma glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) responses during oral glucose tolerance test (OGTT) in 20 lean and 20 obese participants from the Baltimore Longitudinal Study of Aging (BLSA). Next, we recruited 20 healthy men to evaluate GIP and GLP-1 responses during OGTT after administering placebo or nabilone (CBR agonist) in a randomized, double-blind, crossover fashion. Compared with the BLSA lean group, the BLSA obese group had significantly higher fasting and post-OGTT GIP levels, but similar fasting GLP-1 and significantly lower post-OGTT GLP-1 levels. In the nabilone vs. placebo study, when compared with placebo, nabilone resulted in significantly elevated post-dose fasting GIP levels and post-OGTT GIP levels, but no change in post-dose fasting GLP-1 levels together with significantly lower post-OGTT GLP-1 levels. Glucose levels were not different with both interventions. We conclude that elevated GIP levels in obesity are likely a consequence of increased endocannabinoid levels. CBRs exert tonic control over GIP secretion, which may have a homeostatic effect in suppressing GLP-1 secretion. This raises the possibility that gut hormones are influenced by endocannabinoids.

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.

Short-term effects of milkshake containing polydextrose and maltodextrin on subjective feelings of appetite, energy intake and blood glucose in healthy females

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
İsmail Mücahit Alptekin ◽  
Ece Erdoğan ◽  
Aylin İşler ◽  
Esma Cansu Yanalak ◽  
Funda Pınar Çakiroğlu ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Energy Intake ◽  
Postprandial Blood Glucose ◽  
Dietary Fibers ◽  
Analog Scale ◽  
Short Term ◽  
Content Type ◽  
Ad Libitum ◽  
Desire To Eat ◽  
Healthy Females

Purpose Previous studies have reported that dietary fibers such as polydextrose and maltodextrin can reduce food intake; however, the studies on the differences of this effect are insufficient. The purpose of this paper is to compare the effects of dietary fibers maltodextrin and polydextrose on alterations of short-term satiety, energy intake and postprandial blood glucose in healthy females. Design/methodology/approach This study was designed as a randomized, crossover and double blind research. For this purpose, 21 healthy females consumed a milkshake containing 0 g (control), 15 g polydextrose (PDX) and 15 g maltodextrin (MDX), and an ad libitum lunch meal was served 150 min later. Subjective appetite scores (hunger, satiety, prospective food consumption and desire to eat) were measured using a visual analog scale. Appetite scores and blood glucose were measured before preload and once per 15 min after milkshake consumption. Findings Visual analog scale scores showed that PDX had an improved effect on satiety and hunger feelings. Compared to the control, dietary fiber increased the Area Under Curve (AUC) scores of satiety (p < 0.001) and decreased the AUC scores of hunger (p < 0.001), prospective food consumption (p < 0.001) and desire to eat (p < 0.001). Energy intake during ad libitum meal was significantly lower in PDX (Control: 862 (54.3) Kcal versus PDX: 679 (35.4) Kcal and MDX: 780 (49.3) Kcal. Moreover, the blood glucose levels were significantly lower in MDX. Originality/value This study conducted with healthy females demonstrated that PDX was more effective in inducing satiety during subsequent food intake, and that postprandial blood glucose were within more healthy levels in MDX.

scholarly journals Eight-day consumption of inulin added to a yogurt breakfast lowers postprandial appetite ratings but not energy intakes in young healthy females: a randomised controlled trial

2015 ◽  
Vol 115 (2) ◽  
pp. 262-270 ◽  
Author(s):  
Sarah Heap ◽  
Jessica Ingram ◽  
Marron Law ◽  
Amy J. Tucker ◽  
Amanda J. Wright
Keyword(s):  
Energy Intake ◽  
Controlled Trial ◽  
Eating Behaviour ◽  
Hormonal Contraceptives ◽  
Double Blind ◽  
Randomised Controlled ◽  
Desire To Eat ◽  
Repeated Consumption ◽  
Healthy Females

AbstractIncreasing feelings of satiety may reduce appetite and energy intake. The role of inulin consumption in impacting satiety is unclear. A randomised double-blind controlled crossover trial aimed to determine the effects of inulin+yogurt on satiety after 1 and 8-d consumption. The preload breakfast included 100 g vanilla yogurt with (yogurt-inulin (YI)) and without (yogurt-control (YC)) 6 g inulin. A total of nineteen healthy females (22·8 (sd 2·7) years) with non-restrained eating behaviour and taking hormonal contraceptives participated in the study. Day 1 and 8 visual analogue scale (VAS) ratings of Hunger, Fullness, Desire to Eat and Prospective Food Consumption (PFC) were collected at fasting and every 30 min for 180 min. Energy intake was calculated from a weighed ad libitum lunch and remainder of day food records. Total AUC was calculated for each VAS. Day 1 (VAS only) and 8 (VAS and energy intakes) data were compared between YI and YC using ANCOVA, and ANOVA was used to compare energy intakes on Day 1. There were no significant differences between Day 1 YI and YC AUC appetite ratings or energy intakes. However, 8-d consumption of YI v. YC was associated with lower Desire to Eat and PFC ratings but similar lunch and total day energy intakes. Therefore, the addition of 6 g inulin to a commercially available yogurt affected feelings of appetite, but not energy intake, after repeated consumption. These results suggest that inulin may be a suitable ingredient to increase dietary fibre consumption, with potential to impact appetite.

scholarly journals Neurotensin Is Coexpressed, Coreleased, and Acts Together With GLP-1 and PYY in Enteroendocrine Control of Metabolism

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 176-194 ◽  
Author(s):  
Kaare V. Grunddal ◽  
Cecilia F. Ratner ◽  
Berit Svendsen ◽  
Felix Sommer ◽  
Maja S. Engelstoft ◽  
...  
Keyword(s):  
Peptide Yy ◽  
Secretory Granules ◽  
Gut Hormones ◽  
Distal Small Intestine ◽  
Cell Ablation ◽  
Target Organs ◽  
Gut Hormone ◽  
Toxin Receptor ◽  
Functional Consequences ◽  
Glucagon Like Peptide 1

Abstract The 2 gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are well known to be coexpressed, costored, and released together to coact in the control of key metabolic target organs. However, recently, it became clear that several other gut hormones can be coexpressed in the intestinal-specific lineage of enteroendocrine cells. Here, we focus on the anatomical and functional consequences of the coexpression of neurotensin with GLP-1 and PYY in the distal small intestine. Fluorescence-activated cell sorting analysis, laser capture, and triple staining demonstrated that GLP-1 cells in the crypts become increasingly multihormonal, ie, coexpressing PYY and neurotensin as they move up the villus. Proglucagon promoter and pertussis toxin receptor-driven cell ablation and reappearance studies indicated that although all the cells die, the GLP-1 cells reappear more quickly than PYY- and neurotensin-positive cells. High-resolution confocal fluorescence microscopy demonstrated that neurotensin is stored in secretory granules distinct from GLP-1 and PYY storing granules. Nevertheless, the 3 peptides were cosecreted from both perfused small intestines and colonic crypt cultures in response to a series of metabolite, neuropeptide, and hormonal stimuli. Importantly, neurotensin acts synergistically, ie, more than additively together with GLP-1 and PYY to decrease palatable food intake and inhibit gastric emptying, but affects glucose homeostasis in a more complex manner. Thus, neurotensin is a major gut hormone deeply integrated with GLP-1 and PYY, which should be taken into account when exploiting the enteroendocrine regulation of metabolism pharmacologically.

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