Peptide YY release after intraduodenal,intraileal, and intracolonic administration of nutrients in rats

Peptide YY (PYY) release was studied by measuring radioimmunoassayable PYY in the arterial plasma of anaesthetized rats receiving into the duodenum, ileum or colon either a complete semi-liquid meal (3 ml, 21 kJ) or elemental nutrients as isocaloric or isoosmolar solutions. PYY release induced by the intraduodenal meal peaked at 60 min and lasted more than 120 min. The integrated response of PYY over 120 min was larger when the meal was administered into the duodenum than into the ileum. The undigested meal induced no release of PYY over a 120-min period when administered into the colon. When injected into the duodenum in isocaloric amounts to the meal, glucose and amino acids led to the release of as much PYY as did the meal, whereas oleic acid led to the release of less PYY. Part of these responses were due to osmolarity, since administration of intraduodenal hyperosmolar saline led to the release of about half as much PYY as did hyperosmolar glucose. In moderate amounts, and injected as a solution isoosmolar to plasma, oleic acid was a major PYY releaser; the amounts released were at least two times larger when oleic acid was administered into the duodenum than into the ileum and colon. Isoosmolar glucose and amino acids led to the release of no PYY when injected into the duodenum, but were nearly as active as oleic acid in the colon. Short-chain fatty acids induced the release of PYY when injected into the colon, but not into the ileum. Hexamethonium suppressed PYY release induced by the intraduodenal meal, but did not change PYY release induced by glucose or oleic acid in the colon. Urethane anaesthesia did not reduce PYY release induced by the intraduodenal meal. These results suggest that two mechanisms at least contribute to PYY release in the rat. An indirect, neural mechanism, involving nicotinic synapses, is prominent in the proximal small intestine; the stimulation is transmitted to ileal and colonic L-cells by undetermined pathways, but contact of nutrients with L-cells is not needed. Another mechanism, probably direct and quantitatively smaller, occurs in the distal intestine when nutrients come into contact with the mucosa containing L-cells. Glucose, fatty acids and amino acids stimulate differentially the proximal and distal mechanisms.     

Mechanisms of peptide YY release induced by an intraduodenal meal in rats: neural regulation by proximal gut

 Peptide YY (PYY) release in anaesthetized rats was studied during the 2 h following the intraduodenal administration of a semi-liquid meal of 21 kJ. Surgical and pharmacological manipulations were performed in order to analyse the mechanisms of PYY release. Postprandial PYY release was suppressed or strongly decreased by caecocolonectomy, truncal vagotomy, tetrodotoxin, hexamethonium, sensory denervation by perivagal capsaicin, and by the NO-synthase inhibitor L-N-arginine methyl ester, while atropine, adrenergic blockers, antagonists of type-A or type-B cholecystokinin (CCK) receptors or bombesin receptors had no effect. Comparing the digestive transit of the semi-liquid meal with the amount of PYY contained in the small bowel wall showed that nutrients had not reached the area rich in cells containing PYY by 30 min, the time at which there was a large PYY release in plasma. By 120 min, the meal front had travelled 72% of the small intestine length, just beginning to reach the PYY-rich part of the ileum. We conclude that the main postprandial PYY release studied in this model comes from ileal and colonic L-cells indirectly stimulated through a neural mechanism originating in the proximal gut and involving sensory vagal fibres, nicotinic synapses and NO release, while CCK and bombesin do not seem to be physiologically involved. Received: 17 July 1996 / Received after revision: 11 October 1996 / Accepted: 18 October 1996     

Gastrointestinal satiety signals in humans--physiologic roles for GLP-1 and PYY?

The present review summarizes the appetite suppressing effects of PYY and GLP-1 in the regulation of food intake in humans. Current evidence supports a role for gastrointestinal peptides as regulators of satiety. The regulation of satiety is, however, complex and it is not surprising that multiple control systems exist. It is interesting to note that nutrients in the small intestine such as hydrolysis products of fat stimulate the release of satiety peptides such as GLP-1 or PYY that serve as satiety signals. Both peptides, released from L-cells from the gastrointestinal tract by the local action of digested food, exert various regulatory functions: stimulation of insulin secretion and inhibition of glucagon secretion as typical actions of GLP-1, inhibition of gastric emptying, and inhibition of appetite for both GLP-1 and PYY. The review focuses on the question, whether the two peptides are true endocrine factors that act as physiologic, hormonal regulators of appetite.     

The physiology of glucagon-like peptide 1

Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon, the gene which is expressed in these cells. The current knowledge regarding regulation of proglucagon gene expression in the gut and in the brain and mechanisms responsible for the posttranslational processing are reviewed. GLP-1 is released in response to meal intake, and the stimuli and molecular mechanisms involved are discussed. GLP-1 is extremely rapidly metabolized and inactivated by the enzyme dipeptidyl peptidase IV even before the hormone has left the gut, raising the possibility that the actions of GLP-1 are transmitted via sensory neurons in the intestine and the liver expressing the GLP-1 receptor. Because of this, it is important to distinguish between measurements of the intact hormone (responsible for endocrine actions) or the sum of the intact hormone and its metabolites, reflecting the total L-cell secretion and therefore also the possible neural actions. The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the "ileal brake" mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake. Because of these actions, GLP-1 or GLP-1 receptor agonists are currently being evaluated for the therapy of type 2 diabetes. Decreased secretion of GLP-1 may contribute to the development of obesity, and exaggerated secretion may be responsible for postprandial reactive hypoglycemia.     

The developmental plasticity of colocalization pattern of peptide YY and glucagon-like peptide-1 in the endocrine cells of bovine rectum

Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) are produced in endocrine cells that show distal distribution in each of small and large intestine. They are colocalized in the same endocrine cells at different ratios depending on the animal species. The present study examined the possibility of plasticity in the colocalization pattern in the bovine rectum, which is known to contain endocrine cells at a high concentration. Consecutive sections from different pre- and postnatal stages were stained immunohistochemically. The immunoreactive (IR) cells were divided into three groups: 1) cells IR for both PYY and GLP-1 (PYY/GLP-1-IR cells), 2) cells IR only for PYY (PYY-IR cells), and 3) cells IR only for GLP-1 (GLP-1-IR cells). The percentage of PYY/GLP-1-IR cells was high in the prenatal (early, mid- and late fetuses) and suckling stages, whereas it decreased in the herbivorous (weaning, weaned and adult) stages. In contrast, percentages of PYY and GLP-1-IR single cells were low in the prenatal and suckling stages and increased after the suckling stage. PYY/GLP-1 endocrine cells may adapt to the change of digestion depending on feeding habits and/or specific developmental stages of cattle. The present results suggest the developmental plasticity of the colocalization pattern of gut hormones with nutritional transition.     

Nutritional regulation of glucagon-like peptide-1 secretion

Glucagon-like peptide-1 (GLP-1), released from L- cells in the intestinal epithelium, plays an important role in postprandial glucose homeostasis and appetite control. Following the recent therapeutic successes of antidiabetic drugs aimed at either mimicking GLP-1 or preventing its degradation, attention is now turning towards the L-cell, and addressing whether it would be both possible and beneficial to stimulate the endogenous release of GLP-1 in vivo . Understanding the mechanisms underlying GLP-1 release from L-cells is key to this type of approach, and the use of cell line models has led to the identification of a variety of pathways that may underlie the physiological responses of L-cells to food ingestion. This review focuses on our current understanding of the signalling mechanisms that underlie L-cell nutrient responsiveness.     

Effect of gastric distension prior to eating on food intake and feelings of satiety in humans

The factors that regulate food intake and satiation are complex; it has been suggested that signals arising from the small intestine and the stomach play an important role. It is still unknown, to what extent pure mechanical distension of the gastric fundus and antrum can alter food intake. Our aim was therefore to investigate whether transient gastric fundus and antrum distension applied prior to meal ingestion can trigger satiation in healthy humans. Two sequential, randomized, double-blind, four-period cross-over designed studies were performed in 24 healthy male volunteers: (1) 12 subjects underwent four intragastric balloon distension experiments of the fundus (0, 400, 600, 800 ml) before a standard meal intake; (2) 12 subjects underwent intragastric balloon distension experiments of the antrum under the following conditions: 0 ml balloon distension of the antrum plus intraduodenal (ID) saline or ID fat, and 300 ml antrum distension plus ID saline or ID fat. Shortly after the distension period, subjects were free to eat and drink as much as they wished. Neither gastric fundus nor antrum distension showed a reduction in calorie intake. Distending the fundus affected the mean Visual Analogue Scale (VAS) in the premeal period: subjects experienced a reduced degree of hunger and a concomitant feeling of fullness, but the effect was only apparent during distension with a volume of 600 ml or even 800 ml. Cholecystokinin (CCK) and peptide YY (PYY) were not altered by gastric distension. Transient pure mechanical distension of the fundus or the antrum prior to a meal does not trigger satiation.     

Peripheral glucagon-like peptide-1 (GLP-1) and satiation

Peripheral GLP-1 is produced by post-translational processing of pro-glucagon in enteroendocrine L-cells and is released in response to luminal nutrient (primarily carbohydrate and fat) stimulation. GLP-1 is well known for its potent insulinotropic and gluco-regulatory effects. GLP-1 receptors (GLP-1R) are expressed in the periphery and in several brain areas that are implicated in the control of eating. Both central and peripheral administration of GLP-1 have been shown to reduce food intake. Unresolved, however, is whether these effects reflect functions of endogenous GLP-1. Data collected in our laboratory indicate that in chow-fed rats: 1) Remotely controlled, intra-meal intravenous (IV) or intraperitoneal (IP) GLP-1 infusions selectively reduce meal size; 2) hindbrain GLP-1R activation is involved in the eating-inhibitory effect of IV infused GLP-1, whereas intact abdominal vagal afferents are necessary for the eating-inhibitory effect of IP, but not IV, infused GLP-1; 3) GLP-1 degradation in the liver prevents a systemic increase in endogenous GLP-1 during normal chow meals in rats; and 4) peripheral or hindbrain GLP-1R antagonism by exendin-9 does not affect spontaneous eating. Also, although our data indicate that peripheral GLP-1 can act in two different sites to inhibit eating, they argue against a role of systemic increases in endogenous GLP-1 in satiation in chow-fed rats. Therefore, further studies should examine whether a local paracrine action of GLP-1 in the intestine or and endocrine action in the hepatic-portal area is physiologically relevant for satiation.     

Eating rate during a fixed-portion meal does not affect postprandial appetite and gut peptides or energy intake during a subsequent meal

Eating rate has recently been shown to influence energy intake and appetite during an ad libitum meal, and alter postprandial secretion of glucagon-like peptide-1 (GLP-1) and peptide-YY (PYY) following a fixed-portion meal. Whether these effects influence satiety, as measured by energy intake at the subsequent meal, is unclear. We manipulated eating rate during a fixed-portion meal in order to examine how eating behavior and associated periprandial and postprandial responses of putative endocrine mediators of appetite would affect energy intake at the following meal in fifteen non-obese (BMI < 25 kg/m²) and ten obese (BMI ≥ 30 kg/m²) healthy adult men and women. In random order, each participant consumed a standardized, fixed-portion meal in 7 (FM), 14 (MM) or 28 (SM) minutes. Fullness, measured by the Satiety Labeled Intensity Magnitude (SLIM) scale, serum insulin, glucose, leptin, pancreatic polypeptide (PP), PYY, GLP-1, neuropeptide-Y, and plasma cholecystokinin (CCK) were measured for 3 h following the fixed-portion meal. Ad libitum energy intake at the next meal was then measured. Eating slowly delayed time to peak fullness (P ≤ 0.05), but did not alter peak fullness. Peak PP concentrations were attenuated during FM compared to MM and SM (P ≤ 0.05) and were reached earlier during MM compared to SM (P ≤ 0.05). A meal-by-time interaction (P ≤ 0.05), but no differences in AUC, peak, or time to peak were observed for CCK. No additional between meal differences in AUC, peak or time to peak for any endocrine mediator of appetite was observed. Ad libitum energy intake was not different between trials. In conclusion, the rate at which a fixed-portion meal is consumed does not appear to alter satiety despite a small effect on PP and CCK responses.     

Appetite-related gut peptides, ghrelin, PYY, and GLP-1 in obese women with and without binge eating disorder (BED)

BED is characterized by overeating with a loss of control. The primary aim of the study was to measure plasma concentrations of three key gut peptides influencing hunger (ghrelin) and satiety (PYY, GLP-1) to ascertain potential abnormalities in BED. The participants were 10 obese BED and 9 obese nonBED premenopausal women. They did not differ in age, 30.1+/-8.1 SD, BMI, 36.2+/-5.9, or % body fat, 43.3+/-5.7. Following a13-h overnight fast, blood was drawn (-15, 0, 5, 15, 30, 60, 90, 120 min) for measurement of total plasma concentrations of ghrelin, PYY and GLP-1, pre and post ingestion of a nutritionally complete liquid meal (1256 kJ) at 9 am (0-5 min). Ratings of hunger and fullness preceded each blood draw. Ghrelin was significantly lower premeal at -15 min (P=.05) and postmeal at 90 min (P=.027) and 120 min (P=.025) in the BED group as compared to the nonBED group. Ghrelin also declined less postprandially in the BED group (P=.019) with a longer time to the nadir value (P=.004). However, fasting and meal-related changes in levels of PYY and GLP-1 did not differ between the groups nor did ratings of hunger and fullness. Following a randomized cognitive behavior and dietary intervention, the ghrelin values in BED normalized. Prior to treatment, the lower fasting ghrelin in BED may be a consequence of down regulation by overeating. The lack of differences in the satiety promoting hormones, PYY and GLP-1, makes them unlikely contributors to the binge eating in BED.     

CCK, ghrelin, and PYY responses in individuals with binge eating disorder before and after a cognitive behavioral treatment (CBT)

Background

Several abnormalities of peripheral neuropeptide release in obese and obese patients with binge eating disorder (BED) compared to controls have been reported: lower baseline, meal-induced, and post-meal ghrelin concentrations, decreased baseline PYY, and a blunted PYY response to meals. In contrast, obese BED individuals show comparable CCK releases.We aimed at clarifying the role of peripheral hormones in BED, to assess the impact of a cognitive behavioral treatment (CBT) for BED on neuropeptides and to investigate the predictive value of neuropeptide concentrations on binge eating status after treatment.

Methods

Blood samples of 14 female and 4 male overweight to obese participants with BED were collected repeatedly for CCK, PYY, and ghrelin analysis in the morning after an 8-h fasting period. BED participants and 19 controls matched for age and body mass index (BMI) were served a standardized breakfast. The release of neuropeptides was compared to corresponding measures of controls.

Results

Fasting baseline values of all three peptides were comparable between BED participants and controls. BED participants revealed a higher meal-induced increase in CCK and PYY compared to controls, whereas ghrelin was not affected. Following a short-term CBT the neuropeptide concentration of the BED participants was comparable to before CBT. The hormone release prior to treatment had no predictive value on binge eating status after the treatment.

Conclusions

With respect to CCK and PYY our results point to a combined conditioned response from the central nervous system and the gut to initiate the release of satiety hormones in order to prevent further bingeing after initial food intake. The release of neuropeptides does not predict short-term treatment outcome. Future prospective studies should investigate whether neuropeptide secretion influences the course of BED in the long term.     

Different Regulation of Atrial ANP Release through Neuropeptide Y2 and Y4 Receptors

Neuropeptide Y (NPY) receptors are present in cardiac membranes. However, its physiological roles in the heart are not clear. The aim of this study was to define the direct effects of pancreatic polypeptide (PP) on atrial dynamics and atrial natriuretic peptide (ANP) release in perfused beating atria. Pancreatic polypeptides, a NPY Y₄ receptor agonist, decreased atrial contractility but was not dose-dependent. The ANP release was stimulated by PP in a dose-dependent manner. GR 23118, a NPY Y₄ receptor agonist, also increased the ANP release and the potency was greater than PP. In contrast, peptide YY (3-36) (PYY), an NPY Y₂ receptor agonist, suppressed the release of ANP with positive inotropy. NPY, an agonist for Y_{1, 2, 5} receptor, did not cause any significant changes. The pretreatment of NPY (18-36), an antagonist for NPY Y₃ receptor, markedly attenuated the stimulation of ANP release by PP but did not affect the suppression of ANP release by PYY. BIIE0246, an antagonist for NPY Y₂ receptor, attenuated the suppression of ANP release by PYY. The responsiveness of atrial contractility to PP or PYY was not affected by either of the antagonists. These results suggest that NPY Y₄ and Y₂ receptor differently regulate the release of atrial ANP.     

Gastric emptying and symptoms of bulimia nervosa: effect of a prokinetic agent

ObjectivePrevious studies have suggested that delayed gastric emptying and abnormal postprandial release of hormones that influence satiation, particularly cholecystokinin (CCK), may play an important role in the pathophysiology of bulimia nervosa (BN). This study was designed to test these hypotheses as well as the efficacy of the prokinetic agent erythromycin in patients with BN.MethodThirty-two normal-weight women with BN and 24 control participants consumed a large liquid test meal. Gastric emptying and pre- and postprandial release of CCK, peptide YY (PYY), and ghrelin were determined. Participants with BN were then recruited for double-blind treatment with erythromycin up to 500 mg three times daily vs. placebo for 6 weeks, following which they consumed a repeat test meal with gastric emptying and appetitive hormone measurements.ResultsCCK release at 15 min following the meal was marginally lower (p = 0.1) in BN than in control participants. Rate of gastric emptying and postprandial hormone release were similar in BN and controls. BN patients assigned to erythromycin compared to those assigned to placebo had more rapid gastric emptying following treatment, but there were no differences in release of CCK, PYY, or ghrelin following the post-treatment test meal. Moreover, treatment with erythromycin was not associated with clinical response.DiscussionThe current study does not support the clinical utility of moderate dose erythromycin in treating BN. Furthermore, the findings suggest that a modest increase in gastric emptying rate is associated neither with altered postprandial hormonal release nor with clinical benefit in these patients. While providing no evidence for the effectiveness of prokinetic agents in this setting, our findings do not preclude the possibility that a greater increase in gastric emptying rate might prove beneficial.     

Use of satiety peptides in assessing the satiating capacity of foods

Foods differ in their satiating capacity. Satiety peptides may help to provide evidence for biological mechanisms behind these differences. The aim of this paper was to discuss the physiological relevance of three individual appetite peptides, i.e. CCK, GLP-1 and PYY, in assessing the satiating capacity of foods. A literature research was conducted on CCK, GLP-1, PYY and satiety; effective exogenous infusion studies and endogenous production studies, i.e. changes induced by foods, were identified. The relative changes in blood concentrations in these studies were compared in order to assess an indication of the physiological relevance of the peptides. Relative changes in the two types of studies investigating CCK overlapped, i.e. increases in serum were 3 to 14-fold in effective exogenous studies (n=7) and 2 to 8-fold in endogenous production studies (n=9). The relative changes in GLP-1 and PYY did not overlap; GLP-1: 4 to 16 fold in effective exogenous studies (n=4) and no effect to 4 fold in endogenous production studies (n=38). PYY: 3 to 11-fold in effective exogenous studies (n=14) and no effect to 2-fold in endogenous production studies (n=10). GLP-1 and PYY show effects on satiety at supra-physiological dosages, they are not likely to contribute individually to a difference in satiating capacity of foods and can therefore not be interpreted in isolation. The effects of CCK are likely to be in the physiological range and therefore may have an individual contribution to a difference in satiating capacity between foods.     

Production and characterization of four anti-neuropeptide Y monoclonal antibodies.

Human neuropeptide Y (hNPY) is a potent vasoconstrictor peptide of 36 aminoacid residues. We isolated hybridomas secreting four monoclonal antibodies directed against various epitopes of neuropeptide Y and studied their cross-reactivity with peptide YY (PYY) and the pancreatic polypeptide (PP), two peptides sharing sequence homologies with hNPY (respectively 70% and 50%). The antibody NPY02 is an IgG1 with a Ka of 5.5 x 10(10) liters/mol. It binds to the 11-24 region of NPY (IC50 = 2 x 10(-7)M), does not recognize PP but cross-reacts weakly with PYY. Antibodies NPY03 and NPY05 are IgG2 with respective Ka's of 6.7 x 10(9) and 2.5 x 10(10) liters/mol. They interact with a C-terminal epitope on NPY (NPY 27-34, IC50 = 2 x 10(-9) M for NPY03 and NPY 32-36, IC50 = 1 x 10(-9) M for NPY05). These two antibodies cross-react with PYY whereas only NPY05 binds PP. NPY05 is unable to bind the free acid form of neuropeptide Y. The 32-36 COOH free subpeptide is recognized 50,000 less efficiently by NPY05 than its amidated form. Antibody NPY04 is an IgG3 with a Ka of 3.8 x 10(8) liters/mol. It recognizes a N-terminal epitope between aminoacids 1 and 12 (IC50 = 2.5 x 10(-6) M). NPY04 interacts weakly with PYY but not detectably with PP. These results obtained with 4 different monoclonal antibodies demonstrate the presence of at least four epitopes on hNPY, two of them being continuous. These antibodies will be used to study the interaction of NPY with its receptor and to develop sensitive and specific assays for determination of NPY concentrations in biological fluids.     

GLP-1 antagonism with exendin (9-39) fails to increase spontaneous meal size in rats

Intravenous and intraperitoneal (IP) administration of glucagon like peptide-1 (7-36)-amide (GLP-1) inhibits eating, but the physiological relevance of this satiating effect is not yet clear. We addressed this issue by testing the effects of the GLP-1 receptor antagonist exendin 9-39 (Ex (9-39)) on spontaneous eating and on the satiating effect of exogenous GLP-1. Adult, male Sprague-Dawley rats were equipped with chronic IP catheters and received intrameal infusions (0.2 ml/min, 2.5 min) that were remotely triggered 2-3 min after the onset of the first or the second spontaneous nocturnal meal. Infusions of 10, but not 5 or 2.5 nmol/kg body weight (BW) GLP-1 significantly reduced the size of the first spontaneous nocturnal meal compared to vehicle. The first intermeal interval, subsequent meal sizes and cumulative food intake were unchanged by 10 nmol/kg GLP-1. Infusions of 10 or 30 nmol/kg BW Ex (9-39) during the second spontaneous nocturnal meal did not affect the size of that meal and decreased rather than increased meal duration. Co-infusion of 30 nmol/kg BW Ex (9-39) prevented the satiating effect of 10 nmol/kg BW GLP-1 during the first spontaneous nocturnal meal, but again did not increase meal size by itself. That a dose of Ex (9-39) that is sufficient to block the satiating effect of exogenous GLP-1 failed to increase meal size when administered alone under comparable conditions suggests that endogenous intestinal GLP-1 is not required for the control of spontaneous meal size in rats under our conditions. The situations in which GLP-1 is of physiological relevance for satiation require further research.     

Intestinal feedback signaling and satiety

Peptidergic and neural signals arising from the presence of food in the gastrointestinal track provide feedback signals to the brain about the nature and quantity of consumed nutrients. Peptide secreting cells are differentially distributed along the gastrointestinal tract. How ingested nutrients activate or inhibit peptide secretion is complex and depends upon local, hormonal and neural mechanisms. The mode of action of the various peptides is equally complex involving endocrine, paracrine and neurocrine signaling. The success of bariatric surgical approaches to obesity treatment is secondary to alterations in gastrointestinal feedback signaling and roles of increased secretion of lower gut peptides such as peptide YY (PYY) and glucagon like peptide 1 (GLP-1) in mediating the superior effects of Roux-en-Y gastric bypass (RYGB) surgery are becoming evident. Direct nutrient delivery to jejunal sites that models the site of gastric-jejunal anastamosis in RYGB is especially effective at inhibiting food intake. Such infusions also stimulate the release of lower gut peptides suggesting a role for increased gut peptide signaling in sustaining such feeding inhibitions. Thus, gut peptides are clear targets for future obesity therapeutic developments.     

Studies on the inhibition of pancreatic secretion by luminal somatostatin

The effects of somatostatin, instilled into the duodenum or administered intravenously, on pancreatic response to endogenous (meal and duodenal acidification) or exogenous (secretin and caerulein) stimulants were compared in five dogs with gastric and pancreatic fistulas. Somatostatin, whether applied topically to the duodenal mucosa or given intravenously, resulted in qualitatively similar inhibition of pancreatic secretion of water, bicarbonate, and enzyme protein, being about four to eight times less potent after intraduodenal than after intravenous administration. A meal-induced secretion appears to be the most sensitive to the inhibitory action of intraduodenal somatostatin, probably because of the suppression of gastric acid and serum gastrin secretin involved in the postprandial stimulation of the exocrine pancreas. The inhibition of pancreatic secretion by luminal somatostatin was accompanied by a significant increase of plasma levels of the immunoreactive somatostatin, indicating that this peptide can be absorbed intact across the intestinal mucosa. We conclude that somatostatin administered into the gut lumen is absorbed into the circulation and can inhibit pancreatic secretion both by the suppression of the release of gastrointestinal hormones and by direct inhibitory action on the exocrine pancreas.     

Suggestion of new possibilities in approaching individual variability in appetite through constitutional typology: a pilot study

ABSTRACT: BACKGROUND: Appetite is intricately connected to eating behaviors and shows a high individual variability. In an attempt to approach the problem of gut hormone profiles, appetite, and eating behaviors at the individual level, we have adopted a constitutional typing system widely used in traditional East-Asian medicine, the Sasang constitutional typology, in order to determine the individual variations in appetite, eating behavior, and weight change. METHODS: This pilot study was designed to investigate the variability of appetite among individuals by tracking the gut hormone patterns across different constitutional types. Pre- and post-prandial concentrations of anorectic (peptide YY (PYY), glucagon-like peptide 1 (GLP-1)) and orexigenic (active ghrelin) gut hormones were measured in healthy, normal-weight (18.5 kg/m2 [LESS-THAN OR EQUAL TO]BMI <23 kg/m2) male subjects aged 20--35 (Soyang (SY) (n = 9), Taeeum (TE) (n = 9), and Soeum (SE) (n = 10) constitutional types). RESULTS: Significant differences were found only in the PYY concentrations across the three groups (p = 0.031). The PYY concentration peaked at 30-min post-prandial in the SE group and was significantly higher compared to the other two groups (p = 0.004). The GLP-1 concentration peaked at 15-min post-prandial in the SE group (not significant). The ghrelin levels at 30-min pre-prandial were relatively lower in the TE group compared to the other groups (not significant). CONCLUSIONS: In conclusion, although with weak statistical power, meaningful gut hormone patterns specific to each constitutional type were discovered in this pilot study, which could offer a new method of approaching the problem of appetite and eating behavior from the angle of individual variability in appetite.