Release Of Gastrointestinal Peptides Research Articles

Food texture influences on satiety: systematic review and meta-analysis

Obesity is one of the leading causes of preventable deaths. Development of satiety-enhancing foods is considered as a promising strategy to reduce food intake and promote weight management. Food texture may influence satiety through differences in appetite sensations, gastrointestinal peptide release and food intake, but the degree to which it does remains unclear. Herein, we report the first systematic review and meta-analyses on effects of food texture (form, viscosity, structural complexity) on satiety. Both solid and higher viscous food reduce hunger by − 4.97 mm (95% confidence interval (CI) − 8.13, − 1.80) and − 2.10 mm (95% CI − 4.38, 1.18), respectively compared to liquid and low viscous food. An effect of viscosity on fullness (95% CI 5.20 (2.43, 7.97) and a moderate effect of the form of food (95% CI − 26.19 (− 61.72, − 9.35) on food intake were noted. Due to the large variation among studies, the results should be interpreted cautiously and modestly.

Abstract P130: Acute Hyperlipidemia Increases Vasodilation in Conduit Arteries but Has No Effect on Microvascular Recruitment in African American Women

African Americans have one of the highest prevalence of hypertension in the United States. Impaired endothelial function has been implicated in the pathophysiology of hypertension in this group. We previously reported that brachial artery diameter increases from 3.9±0.14 to 4.1± 0.14 at 4 hours after ingestion of a high fat meal, suggesting vasodilation of conduit arteries. Considering that oral fat ingestion stimulates the release of gastrointestinal peptides with vasoactive properties, we aimed to isolate the vascular effect of fat on conduit artery and microvasculature by inducing an acute elevation of triglycerides and free fatty acids with an infusion of 20% intralipid® and heparin. To assess endothelial function we measured changes in the diameter of the brachial artery to hyperemia with a continuous edge detection and wall tracking software. Effect on microvasculature was obtained with contrast-enhanced ultrasonography (CEU) of the brachioradialis muscle with lipid-perflutren microbubbles infusion. We studied 14 obese healthy African American women, age 39± 10, BMI 38.7± 3.4 kg/m. 2 Triglycerides increased from 60.7±30.5 to 523.3±231 mg/dL at the end of the 4 h infusion. Brachial artery diameters were 3.6±0.16 and 3.9±0.18 mm at baseline, and 4-h, P=0.109, respectively. Flow mediated dilation improved at the end of the 4-h infusion period (4.3±0.95 to 6.2±1.21%, P=0.016), figure . Microvascular blood volume did not change with the intervention 5.8±4.9 vs. 5.9±3.6, P=0.55. In conclusion, IV acute hyperlipidemia did not increase brachial artery diameter nor microvascular circulation, however it potentiates vascular reactivity in conduit arteries.

The effect of bitter, umami and sweet tastants on the food intake regulation

Background. In the past decades, the prevalence of obesity and overweight has risen to epidemic dimensions. Nowadays, there is a great demand for new and efficient treatments to decrease this prevalence. Literature revealed, that the gastrointestinal tract contains taste receptors, similar to those present on the tongue, which may have an influence on the regulation of food intake and energy expenditure. However the exact working mechanism is unknown. Objective. This study investigated, the effects of the bitter-, sweet-, umami tastants and a combination of those on ad libitum food intake and gastrointestinal hormone release. Hypothesis. We hypothesized that an intraduodenal infusion of the bitter, umami and sweet tastants and a combination of these tastants, results in a significant reduction in food intake and an significant increase in the release of the gastrointestinal peptides GLP-1 and CCK. Furthermore, the largest reduction on ad libitum food intake, will be achieved by the combination treatment, because this will stimulate multiple taste receptors instead of just one group. Finally, a bitter infusion will induce greater effects on the ad libitum food intake and gastrointestinal hormone release, compared to the sweet and umami tastants. This because the bitter receptor is more sensitive to sense its tastant compared to the others.Methods. In this double blind, randomized, placebo controlled, cross-over study, we tested 15 healthy volunteers (Men: 5; Age 23.94±1.97 years; BMI 22.43±0.33 kg/m2 ). The study consisted of five identical test days. During these days, the effects of the tastants umami (Monosodium glutamate), sweet (Rebaudioside A), bitter (Quinine), a combination of these tastants and the placebo (tap water) treatment, were collected. This by infusing them into the duodenum by means of a nasoduodenal tube. Furthermore, multiple blood samples were drawn before, during and after the infusions to determine gastrointestinal peptide release of GLP-1 and CCK into the blood. Finally, an ad libitum pasta meal was provided to define the effects of the tastants on ad libitum meal intake.

Small intestinal protein infusion in humans: evidence for a location-specific gradient in intestinal feedback on food intake and GI peptide release.

Protein infusion in the small intestine results in intestinal brake activation: a negative feedback mechanism that may be mediated by the release of gastrointestinal peptides resulting in a reduction in food intake. It has been proposed that duodenum, jejunum and ileum may respond differently to infused proteins. To investigate differences in ad libitum food intake, feelings of hunger and satiety and the systemic levels of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), glucose and insulin after intraduodenal, intrajejunal and intraileal protein infusion. Fourteen subjects (four male, mean age: 23±2.1 years, mean body mass index: 21.6±1.8 kg m-2) were intubated with a naso-ileal catheter in this double-blind, randomized, placebo-controlled crossover study. Test days (four in total, executed on consecutive days) started with the ingestion of a standardized breakfast, followed by the infusion of 15 g of protein in the duodenum, jejunum or ileum over a period of 60 min. Food intake was measured by offering an ad libitum meal and Visual Analogue Scale (VAS) scores were used to assess feelings of hunger and satiety. Blood samples were drawn at regular intervals for CCK, GLP-1, PYY, glucose and insulin analyses. Intraileal protein infusion decreased ad libitum food intake compared with both intraduodenal and placebo infusion (ileum: 628.5±63 kcal vs duodenum: 733.6±50 kcal, P<0.01 and placebo: 712.2±53 kcal, P<0.05). GLP-1 concentrations were increased after ileal infusion compared with jejunal and placebo infusion, whereas CCK concentrations were only increased after intraileal protein infusion compared with placebo. None of the treatments affected VAS scores for hunger and satiety nor plasma concentrations of PYY and glucose. Protein infusion into the ileum decreases food intake during the next meal compared with intraduodenal infusion, whereas it increases systemic levels of GLP-1 compared with protein infusion into the jejunum and placebo respectively.

The amount and types of fatty acids acutely affect insulin, glycemic and gastrointestinal peptide responses but not satiety in metabolic syndrome subjects.

Limited clinical evidence is available on the effects of amount and types of dietary fats on postprandial insulinemic and gastrointestinal peptide responses in metabolic syndrome subjects. We hypothesized that meals enriched with designated: (1) amount of fats (50 vs 20g), (2) fats with differing fatty acid composition (saturated, SFA; monounsaturated, MUFA or n-6 polyunsaturated fatty acids, PUFA) would affect insulinemic and gastrointestinal peptide releases in metabolic syndrome subjects. Using a randomized, crossover and double-blinded design, 15 men and 15 women with metabolic syndrome consumed high-fat meals enriched with SFA, MUFA or n-6 PUFA, or a low-fat/high-sucrose (SUCR) meal. C-peptide, insulin, glucose, gastrointestinal peptides and satiety were measured up to 6h. As expected, SUCR meal induced higher C-peptide (45%), insulin (45%) and glucose (49%) responses compared with high-fat meals regardless of types of fatty acids (P < 0.001). Interestingly, incremental area under the curve (AUC0-120min) for glucagon-like peptide-1 was higher after SUCR meal compared with MUFA (27%) and n-6 PUFA meals (23%) (P = 0.01). AUC0-120min for glucose-dependent insulinotropic polypeptide was higher after SFA meal compared with MUFA (23%) and n-6 PUFA meals (20%) (P = 0.004). Significant meal x time interaction (P = 0.007) was observed for ghrelin, but not cholecystokinin and satiety. The amount of fat regardless of the types of fatty acids affects insulin and glycemic responses. Both the amount and types of fatty acids acutely affect the gastrointestinal peptide release in metabolic syndrome subjects, but not satiety.

Capsaicin-induced satiety is associated with gastrointestinal distress but not with the release of satiety hormones

Capsaicin, which is the major pungent principle in chili peppers, is able to induce satiety and reduce caloric intake. The exact mechanism behind this satiating effect is still unknown. We hypothesized that capsaicin induces satiety through the release of gastrointestinal peptides, such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), from enteroendocrine cells in the small intestine. We investigate the effects of an intraduodenal capsaicin infusion (1.5 mg pure capsaicin) in healthy volunteers on hunger, satiety, and gastrointestinal symptoms and the release of GLP-1 and PYY. Thirteen participants (7 women) [mean ± SEM age: 21.5 ± 0.6 y; body mass index (in kg/m(2)): 22.8 ± 0.6] participated in this single-blind, randomized, placebo-controlled crossover study with 2 different treatments. During test days, an intraduodenal infusion of either capsaicin or a placebo (physiologic saline) was performed with the use of a nasoduodenal catheter over a period of 30 min. Visual analog scale scores were used to measure hunger, satiety, and gastrointestinal symptoms. Blood samples were drawn at regular intervals for GLP-1 and PYY. Gallbladder volumes were measured with the use of real-time ultrasonography. The intraduodenal capsaicin infusion significantly increased satiety (P-treatment effect < 0.05) but also resulted in an increase in the gastrointestinal symptoms pain (P-treatment × time interaction < 0.0005), burning sensation (P-treatment × time interaction < 0.0001), nausea (P-treatment × time interaction < 0.05), and bloating (P-treatment × time interaction < 0.001) compared with the effects of the placebo infusion. Satiety scores had a positive correlation with all gastrointestinal symptoms. No differences in GLP-1 and PYY concentrations and gallbladder volumes were observed after the capsaicin infusion compared with after the placebo infusion. An intraduodenal infusion of capsaicin significantly increases satiety but does not affect plasma concentrations of GLP-1 and PYY. Rather, the effect on satiety seems related to gastrointestinal stress as shown by the associations with pain, burning sensation, nausea, and bloating scores. This trial was registered at clinicaltrials.gov as NCT01667523.

Intraduodenal infusion of a combination of tastants decreases food intake in humans

Taste receptors are expressed not only in taste buds but also in the gastrointestinal tract. It has been hypothesized that these receptors may play a role in satiety and food intake. This study investigated the effect of intraduodenal tastant infusions (bitter, sweet, and umami) on food intake, hunger and fullness, gastrointestinal symptoms, and gastrointestinal peptide release. Fifteen healthy volunteers [6 male; mean ± SEM age: 23.9 ± 2.0 y; mean ± SEM body mass index (in kg/m(2)): 22.4 ± 0.3] received 5 treatments in a double-blind, randomized, placebo-controlled crossover design. Test days started with the insertion of a nasoduodenal catheter followed by a standardized liquid breakfast. Participants received an intraduodenal infusion 150 min after breakfast, containing quinine (bitter), rebaudioside A (sweet), monosodium glutamate (umami), a combination of the 3 tastants, or placebo (tap water) over a period of 60 min. Food intake was measured during an ad libitum meal, and visual analog scales were used to monitor gastrointestinal complaints and hunger and fullness scores. Blood samples were drawn at regular intervals for cholecystokinin, glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) analysis. Infusion of the combination of tastants substantially decreased food intake (422 ± 97 compared with 486 ± 104 kcal for placebo, P < 0.05), whereas both a combination of tastants and umami decreased hunger scores compared with placebo. No change in cholecystokinin, GLP-1, or PYY concentrations was observed during the infusions. Intraduodenal infusions of the tastants did not result in gastrointestinal symptoms. Intraduodenal infusion of umami and a combination of tastants inhibits feelings of hunger, but only the latter also reduces food intake. However, these alterations were not accompanied by changes in the plasma concentrations of the gut-derived peptides cholecystokinin, GLP-1, or PYY. This trial was registered at clinicaltrials.gov as NCT01956838.

Effects of meal size on the release of GLP-1 and PYY after Roux-en-Y gastric bypass surgery in obese subjects with or without type 2 diabetes.

Changes in gastrointestinal peptide release may play an important role in improving glucose control and reducing body weight following Roux-en-Y gastric bypass (RYGB), but the impact of low caloric intake on gut peptide release post-surgery has not been well characterized. The purpose of this study was to assess the relationships between low caloric intake and gut peptide release and how they were altered by RYGB. Obese females including ten normoglycemic (ON) and ten with type 2 diabetes mellitus (T2DM) (OD) were studied before, 1 week, and 3 months after RYGB. Nine lean, normoglycemic women were studied for comparison. Subjects were given three separate mixed meal challenges (MMCs; 75, 150, and 300 kcal). Plasma glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were analyzed. Prior to surgery, only minimal increases in GLP-1 and PYY were observed in response to the MMCs. After surgery, the peak GLP-1 concentration was progressively elevated in response to increasing meal sizes. The meal sizes had a statistically significant impact on elevation of GLP-1 incremental areas under the curve (ΔAUC) in both ON and OD at 1 week and 3 months post-surgery visits (p < 0.05 for all comparisons). The PYY ∆AUC was also significantly increased in a meal size-dependent manner in both ON and OD at both post-surgery visits (p < 0.05 for all comparisons). Meal sizes as small as 75-300 kcal, which cause minimal stimulation in GLP-1 or PYY release in the subjects before RYGB, are sufficient to provide statistically significant, meal size-dependent increases in the peptides post-RYGB both acutely and after meaningful weight loss occurred.

Ileal brake activation: macronutrient-specific effects on eating behavior?

Activation of the ileal brake, by infusing lipid directly into the distal part of the small intestine, alters gastrointestinal (GI) motility and inhibits food intake. The ileal brake effect on eating behavior of the other macronutrients is currently unknown. The objective of this study was to investigate the effects of ileal infusion of sucrose and casein on food intake, release of GI peptides, gastric emptying rate and small-bowel transit time with safflower oil as positive control. This randomized, single-blind, crossover study was performed in 13 healthy subjects (6 male; mean age 26.4±2.9 years; mean body mass index 22.8±0.4 kg m(-2)) who were intubated with a naso-ileal catheter. Thirty minutes after the intake of a standardized breakfast, participants received an ileal infusion, containing control ((C) saline), safflower oil ((HL) 51.7 kcal), low-dose casein ((LP) 17.2 kcal) or high-dose casein ((HP) 51.7 kcal), low-dose sucrose ((LC) 17.2 kcal) and high-dose sucrose ((HC) 51.7 kcal), over a period of 90 min. Food intake was determined during an ad libitum meal. Visual analogue score questionnaires for hunger and satiety and blood samples were collected at regular intervals. Ileal infusion of lipid, protein and carbohydrate resulted in a significant reduction in food intake compared with control (HL: 464.3±90.7 kcal, P<0.001; HP: 458.0±78.6 kcal, P<0.005; HC: 399.0±57.0 kcal, P<0.0001 vs control: 586.7±70.2 kcal, P<0.001, respectively). A reduction in energy intake was still apparent when the caloric amount of infused nutrients was added to the amount eaten during the ad libitum meal.Secretion of cholecystokinin and peptide YY but not of glucagon-like peptide-1 (7-36) was increased during ileal perfusion of fat, carbohydrates and protein. During ileal perfusion of all macronutrients, a delay in gastric emptying and intestinal transit was observed, but differences were not significant compared with control. Apart from lipids, also sucrose and casein reduce food intake on ileal infusion, thereby activating the ileal brake. In addition to food intake, also satiety and GI peptide secretion were affected.

A randomised trial of enteric-coated nutrient pellets to stimulate gastrointestinal peptide release and lower glycaemia in type 2 diabetes

Glucagon-like peptide-1 (GLP-1), an important mediator of postprandial glycaemia, could potentially be stimulated by delivering small quantities of nutrient to a long length of distal gut. We aimed to determine whether enteric-coated pellets, releasing small amounts of lauric acid throughout the ileum and colon, could reduce glycaemic responses to meals in type 2 diabetes, associated with stimulation of GLP-1. Eligible patients, who had type 2 diabetes controlled by diet or metformin, were each studied on two occasions in a hospital setting. After an overnight fast, patients consumed 5 g active pellets (47% lauric acid by weight) or placebo with breakfast (T = 0 min) and lunch (T = 240 min), in a crossover design with order randomised by the hospital pharmacy and allocation concealed by numbered containers. Patients and investigators making measurements were blinded to the intervention. Blood was sampled frequently for blood glucose (the primary outcome) and hormone assays. Eight patients were randomised (four to receive either intervention first), and all completed the study without adverse effects. Blood glucose was lower after breakfast (T = 0-240 min, area under the curve (AUC) 2,075 ± 368 vs 2,216 ± 163 mmol/l × min) and lunch (T = 240-480 min, AUC 1,916 ± 115 vs 2,088 ± 151 mmol/l × min) (p = 0.02 for each) after active pellets than after placebo. Plasma GLP-1 concentrations were higher after breakfast (p = 0.08) and lunch (p = 0.04) for active pellets. While there were no differences in insulin or glucose-dependent insulinotropic polypeptide concentrations, glucagon concentrations were higher after breakfast and lunch (p = 0.002 for each) for active pellets. Delivering small amounts of nutrient to the ileum and colon can stimulate substantial endogenous GLP-1 release and attenuate postprandial glycaemia. This novel approach has therapeutic potential in type 2 diabetes. Australian New Zealand Clinical Trials Registry ACTRN12612000600842. The study was funded by Meyer Nutriceuticals.

Role Played by Afferent Signals from Olfactory, Gustatory and Gastrointestinal Sensors in Regulation of Autonomic Nerve Activity

Afferent signals from the olfactory system, gustatory system and gastrointestinal (GI) tract control visceral functions such as oral and gut secretions and several digestive, endocrine, thermogenic, cardiovascular and renal responses via autonomic reflexes. It is well known that odors and tastes, such as umami, can stimulate oral and GI secretions to improve food intake and digestion in a process termed the cephalic phase response. The perception of GI nutrients, such as carbohydrates and amino acids, can control food digestion, absorption and utilization via the vago-vagal reflex during a meal. Recent advances in understanding the molecular physiology of taste indicate that taste receptors able to sense such nutrients are widely distributed in the GI tract, including the oral cavity. These receptors act as nutrient sensors to trigger food digestion, the release of GI peptides and the formation of food preferences. In this paper, we review recent evidence on the regulation of GI functions by the autonomic nervous system via peripheral odor and nutrient sensors.

Circadian variation of rectal sensitivity and gastrointestinal peptides in healthy volunteers

The aim of our study was to identify diurnal variation of perception of rectal distension and the release of gastroenteropancreatic hormones. In 12 healthy male volunteers (25 years, range 22-32), a rectal balloon distension was performed. Rectal perception thresholds (minimal, urge and pain) and rectal compliance were double-measured with a computer-controlled barostat at seven standardized time points during the day (from 16.00 to 14.00 hours the following day). Blood samples were taken 30 min before and after each rectal distension procedure to determine plasma levels of cholecystokinin (CCK), pancreatic polypeptide (PP) and motilin. Sensory thresholds for urge and pain varied significantly with the time of day, with higher threshold levels in the evening than in the morning hours. Bowel wall compliance showed as well-significant variance at pain threshold and was higher during daytime than in the evening or at night. In contrast to motilin, release of CCK and PP also showed a significant variation depending on daytime. Perception of rectal distension stimuli as well as compliance was independent of intake of food and peptide hormone levels, but CCK and PP levels increased with food, and PP levels decreased with rectal distension. Significant differences in the perception of rectal distension stimuli for urge and pain depending on daytime were found, but the release of gastrointestinal peptides seemed not to be involved. This circadian variation needs to be taken into account in patients and volunteer studies.

Effect of protein, fat, carbohydrate and fibre on gastrointestinal peptide release in humans

Short-term regulation of food intake controls what, when and how much we eat within a single day or a meal. This regulation results from an integrated response to neural and humoral signals that originate from the brain, gastrointestinal (GI) tract and adipose tissue. In the GI tract, multiple sites including the stomach, duodenum, distal small intestine, colon, and pancreas are involved in this process. Ingested food evokes satiety by mechanical stimulation and by release of peptides in the GI tract. The intestine in particular plays a key role in satiety through various peptides secreted in response to food. Many of the intestinal peptides inhibit also gastric emptying thus enhancing gastric mechanoreceptor stimulation. In this review, the current knowledge about the effects of different macronutrients and fibre on the release of GI satiety-related peptides in humans is discussed.

Impact of Gastric Bypass Surgery on Gut Hormones and Glucose Homeostasis in Type 2 Diabetes

Gastric bypass surgery (GBP) for obesity, by constructing an isolated ∼30-ml proximal gastric pouch connected to a 75-cm limb of proximal jejunum, bypassing &amp;gt;90% of the stomach, the pylorus, and the duodenum, cures type 2 diabetes in &amp;gt;80% of cases. We review alterations in gastrointestinal peptide release after GBP that affect glucose disposal. We focus on ghrelin and the incretins glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and peptide YY as the most likely candidates for increasing insulin sensitivity after these operations, even before substantial weight loss has occurred. Although we have limited our review to only four gastrointestinal peptides, others may be involved, as are adipocyte-derived molecules such as leptin and adiponectin, and substrate receptor interactions in target tissues including the brain.

Dietary lactitol fermentation increases circulating peptide YY and glucagon-like peptide-1 in rats and humans

Objective Recently peptide YY (PYY) has attracted interest as a possible regulator of food intake. Release of PYY by nutrients in the distal small intestine is thought to contribute to the so-called ileal brake by inhibiting motility and secretion in the foregut. Our objective was to establish whether plasma concentrations of the gut peptides PYY and glucagon-like peptide-1 in rats and humans change in response to intake of a non-absorbable but fermentable carbohydrate. Methods The acute response was determined in rats by killing animals 0, 5, 10, and 24 h after a single meal with or without lactitol (100 g/kg of semisynthetic diet) and measuring PYY and glucan-like peptide-1 concentrations in plasma. Food intake, body mass, and plasma peptide levels were also determined in rats fed the same diet for 10 d. Healthy human volunteers consumed lactitol or sucrose as a fruit-flavored drink. Breath hydrogen levels were measured at 45-min intervals over the next 7.5 h and plasma peptide concentrations were assessed after 0 and 5 h. Volunteers were also asked to complete a questionnaire to record satiety and well-being. Results Ingestion of lactitol significantly increased the acute postprandial PYY response in rats, and prolonged consumption decreased weight gain in growing rats. In humans given a single dose of lactitol, the effects on PYY were much less marked but the postprandial decrease in circulating concentrations of PYY was attenuated. There was no effect on plasma glucan-like peptide-1. Conclusion Our observations are consistent with a role for fermentation products in the release of gastrointestinal peptides in the rat and, to a lesser extent, in humans.

Effect of rectal distension on gallbladder emptying and circulating gut hormones

Abnormalities of upper gut motility, including a delay of gastric emptying and small bowel transit, found in patients with constipation may be secondary to factors originating in the colon or rectum as a result of faecal stasis. The aim was to determine if stimulation of mechanosensory function by rectal distension affects postprandial gallbladder emptying and release of gastrointestinal peptides participating in control of upper gut motility. Eight healthy volunteers were studied with an electronic barostat and a plastic bag positioned in the rectum. Intrabag pressure was maintained at minimal distension pressure + 2 mmHg on one occasion and on a pressure that induced a sensation of urge on the other. Gallbladder volume and plasma concentrations of cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY (PYY) were measured before and after ingestion of a 450-kcal mixed liquid meal. Rectal distension enhanced maximum gallbladder emptying from 66 +/- 7% to 78 +/- 5% (P < 0.05). Distension tended to increase integrated plasma PYY from 77 +/- 30 pM min to 128 +/- 40 pM min in the first hour after the meal (P = 0.08) and it suppressed integrated plasma PP from 1133 +/- 248 pM min to 269 +/- 284 pM min in the second hour (P < 0.05). Integrated plasma CCK concentrations were not significantly affected. Mechanosensory stimulation of the rectum enhances postprandial gallbladder emptying and influences postprandial release of gut hormones involved in the regulation of gastrointestinal motility in healthy subjects. These mechanisms may play a role in the pathogenesis of the upper gastrointestinal motor abnormalities observed in constipated patients.

Effect of rectal distension on gallbladder emptying and circulating gut hormones

Abnormalities of upper gut motility, including a delay of gastric emptying and small bowel transit, found in patients with constipation may be secondary to factors originating in the colon or rectum as a result of faecal stasis. The aim was to determine if stimulation of mechanosensory function by rectal distension affects postprandial gallbladder emptying and release of gastrointestinal peptides participating in control of upper gut motility. Eight healthy volunteers were studied with an electronic barostat and a plastic bag positioned in the rectum. Intrabag pressure was maintained at minimal distension pressure + 2 mmHg on one occasion and on a pressure that induced a sensation of urge on the other. Gallbladder volume and plasma concentrations of cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY (PYY) were measured before and after ingestion of a 450-kcal mixed liquid meal. Rectal distension enhanced maximum gallbladder emptying from 66 ± 7% to 78 ± 5% (P < 0·05). Distension tended to increase integrated plasma PYY from 77 ± 30 pM min to 128 ± 40 pM min in the first hour after the meal (P = 0·08) and it suppressed integrated plasma PP from 1133 ± 248 pM min to 269 ± 284 pM min in the second hour (P < 0·05). Integrated plasma CCK concentrations were not significantly affected. Mechanosensory stimulation of the rectum enhances postprandial gallbladder emptying and influences postprandial release of gut hormones involved in the regulation of gastrointestinal motility in healthy subjects. These mechanisms may play a role in the pathogenesis of the upper gastrointestinal motor abnormalities observed in constipated patients.

Synergistic stimulation of CCK secretion from STC-1 cells by sodium oleate and amino acids

A mixed meal is a potent stimulant for the release of gastrointestinal peptides. Fatty acids and amino acids (AA)are digested products of food that stimulate CCK secretion. The postprandial concentration of these nutrients in the intestinal lumen may not be comparable to those during intraduodenal infusion to demonstrate their secretagogue activity. Sodium oleate (SO) and AA have been shown to stimulate STC-l cells to secrete CCK. We hypothesized that these nutrients may act synergistically on CCK cells at subthreshold concentrations. Purpose: To investigate whether or not low doses of SO and AA (L-Trp and L-Phe)can act synergistically on CCK release from STC-l cells. Methods: STC-I cells were incubated without or with SO, L-Trp or L-Phe, or combination of SO with either AA in the absence or presence of different protein kinase inhibitors. The release of CCK in the medium was assessed by a specific RIA. The effect of SO and amino acid on intracellular Ca + concentration ([Ca +L) was determined spectrafluorometrically in Fura 2 AM-preloaded cells. Results: There was a significant synergistic stimulation of CCK release by SO and TrplPhe as demonstrated by the difference between their combinational stimulation and the sum of their individual effects shown in the Table below. The synergism was also timeand dose-dependent. There was no synergistic increase in [Ca+L level between SO (0.14 mM) and Phe (10 mM). The PKC inhibitor, staurosporine (10 nM)did not significantly inhibit each amino acid stimulated CCK release but significantly reduced their synergism with SO. On the other hand, the calmodulin antagonist, calmidazolium chloride did not significantly affect the synergistic effect between SO and amino acids. Conclusion: Combination of SO and TrplPhe synergistically stimulated CCK release from STC-I cells timeand dose-dependently. The synergism appears to be mediated by PKC rather than by Ca+{calmodulin-dependent protein kinase II nor the elevation of [Ca2+L known to mediate stimulation by SO. 599

Disturbed release of gastrointestinal peptides in anorexia nervosa and in obesity.

It is commonly accepted that some neuropeptides play an important role in the control of appetite and hormonal secretion. Several gastrointestinal peptides may affect on central control of appetite via vagal and spinal nerves. The aim of this study was to evaluate the release of gastrointestinal peptides in anorexia nervosa and in obesity, because in these diseases the disturbances in the control of appetite and hormonal secretion were found. Material consisted of 30 women with anorexia nervosa aged 16-29 years (mean 22 years) and 23 women with obesity aged 19-33 years (mean 29 years) and 25 lean women of control group. In women with anorexia nervosa as compared with control group we observed a significant increase of plasma vasoactive intestinal peptide (VIP) levels (p < 0.01) and a significant decrease of leptin (p < 0.001), beta-endorphin (p < 0.01), gastrin (p < 0.05), cholecystokinin (CCK; p < 0.05) and somatostatin (S-S; p < 0.01). In obese women we found a significant increase of neuropeptide Y (NPY; p < 0.001), leptin (p < 0.01), galanin (p < 0.001), beta-endorphin (p < 0.001), gastrin (p < 0.01), CCK (p < 0.001) and S-S (p < 0.01) and a significant decrease of VIP concentrations (p < 0.001) as compared with control group. Our results indicate that the release of gastrointestinal peptides is disturbed in obesity and in anorexia nervosa. These findings suggests that dysfunction of brain-gut axis may be also an important factor in the abnormal control of appetite axcept of hypothalamic dysfunction.

Microflora modulates endocrine cells in the gastrointestinal mucosa of the rat

Background/Aims: Gastrointestinal peptides and biogenic monoamines participate in the regulation of gastrointestinal functions. The aim of this study was to examine the influence of the microflora on the distribution of endocrine cells and on the release of gastrointestinal peptides. Methods: A quantitative morphological study using stereological methods was performed in gastrointestinal sections of conventional and germfree rats. Tissue and plasma concentrations of peptides were measured. Results: The total volumes of gastrin- and serotonin-immunoreactive cells were significantly increased in the gastric mucosa of germfree rats (P < 0.05), as well as the total volumes of serotonin-and motilin-immunoreactive cells in the ileum (P < 0.05) and serotonin-immunoreactive cells in the colonic mucosa (P < 0.05). The tissue concentration of somatostatin was significantly higher in the jejunum (P < 0.05) and lower in the ileum of germfree rats than in controls (P < 0.05). Plasma glucagon was significantly increased in germfree rats (P < 0.05). The total volume of the fundic mucosa was enlarged in germfree rats (P < 0.05), whereas the total volume, the mucosal thickness, and the number of crypt cells of the colonic mucosa were significantly reduced in these rats compared with controls (P < 0.05). Conclusions: Our findings suggest that the intraluminal microflora influences the release of biologically active peptides and that it participates in the regulation of gastrointestinal endocrine cells and the epithelial structure.